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    The EU Clinical Trials Register currently displays   36818   clinical trials with a EudraCT protocol, of which   6079   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-005066-22
    Sponsor's Protocol Code Number:CTSU_MDCO-PCS-17-01
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-04-16
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-005066-22
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research study to find out whether inclisiran sodium, given as injection under the skin every 6 months for about 5 years, helps to prevent heart attacks, strokes or the need for urgent procedures to unblock the arteries supplying the heart, in people who already have vascular disease.
    A.3.2Name or abbreviated title of the trial where available
    ORION-4
    A.4.1Sponsor's protocol code numberCTSU_MDCO-PCS-17-01
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity of Oxford
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    B.Sponsor: 2
    B.1.1Name of SponsorThe Medicines Company
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportThe Medicines Company
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameInclisiran for Injection
    D.3.2Product code Inclisiran for Injection
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNINCLISIRAN
    D.3.9.1CAS number 1639324-58-5
    D.3.9.2Current sponsor codeInclisiran sodium
    D.3.9.3Other descriptive nameALN-60212
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Atherosclerotic cardiovascular disease
    E.1.1.1Medical condition in easily understood language
    Circulatory problems (such as heart attacks and strokes) caused by narrowing of the vessels supplying blood to the brain, heart and other organs
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10051615
    E.1.2Term Atherosclerotic cardiovascular disease
    E.1.2System Organ Class 100000004866
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of ORION-4 is to determine the effect of inclisiran sodium, given 3 times in the first year and then 6 monthly for a total of around 5 years, on 'major adverse cardiovascular events' (defined as any occurrence of non-fatal myocardial infarction [heart attack], death from coronary disease, ischaemic stroke [stroke due to insufficient blood supply rather than bleeding] or urgent coronary revascularization procedure [angioplasty or bypass surgery]) during the scheduled treatment period.
    E.2.2Secondary objectives of the trial
    The secondary objectives include the assessment of the effect of inclisiran on;
    (1) A composite of myocardial infarction (heart attack) or death from coronary disease
    (2) Cardiovascular death.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    (1) Age ≥55 years
    (2) History or evidence of at least one of the following:
    Myocardial infarction
    Ischaemic stroke
    Peripheral arterial disease (evident by lower extremity artery revascularization or aortic aneurysm repair)
    E.4Principal exclusion criteria
    (1) Acute coronary syndrome or stroke less than 4 weeks before the Screening visit or during the Run-in period;
    (2) Coronary revascularization procedure planned within the next 6 months;
    (3) Known chronic liver disease;
    (4) Current or planned renal dialysis or transplantation;
    (5) Previous exposure to inclisiran or participation in a randomized trial of inclisiran;
    (6) Previous, current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran;
    (7) Known to be poorly compliant with clinic visits or prescribed medication;
    (8) 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);
    (9) Women of child-bearing potential (unless using adequate contraception); or
    (10) Current participation in a clinical trial with an unlicensed drug or device.
    (11) Staff personnel directly involved with the study and any family member of the investigational study staff

    Those with a capillary blood point-of-care total cholesterol of less than 4 mmol/l at Screening will not be eligible to continue in the study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary assessment will involve an intention-to-treat comparison among all randomized participants of the effects of allocation to inclisiran versus placebo on time to first occurrence of major adverse cardiovascular events (MACE, defined as coronary heart disease death, myocardial infarction, fatal or non-fatal ischaemic stroke, or urgent coronary revascularization procedure) during the scheduled treatment period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The analysis will be undertaken at the end of the study after an average follow-up of 5 years and will include primary outcomes which have occurred during the scheduled follow-up period.
    E.5.2Secondary end point(s)
    Secondary assessments will involve intention-to-treat comparisons among all randomized participants of the effects of allocation to inclisiran versus placebo during the scheduled treatment period on time to first occurrence of:

    (i) The composite outcome of coronary heart disease death or myocardial infarction; and

    (ii) Cardiovascular death.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The analysis will be undertaken at the end of the study after an average follow-up of 5 years and will include secondary outcomes which have occurred during the scheduled follow-up period.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned100
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days31
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 7500
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 7500
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state12000
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12000
    F.4.2.2In the whole clinical trial 15000
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    At the conclusion of the study, all patients will be able to continue with their usual lipid lowering treatment from their GP or consultant. Inclisiran sodium does not have a marketing authorisation and so will not be available to participants after the study.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-06-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-31
    P. End of Trial
    P.End of Trial StatusOngoing
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