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    Summary
    EudraCT Number:2020-005176-35
    Sponsor's Protocol Code Number:ESR-19-20262
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2020-11-05
    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 ConcernedSweden - MPA
    A.2EudraCT number2020-005176-35
    A.3Full title of the trial
    OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosili-cate in Heart Failure (OPRA-HF)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Optimizing medical therapy in patients with heart failure
    A.3.2Name or abbreviated title of the trial where available
    OPRA-HF
    A.4.1Sponsor's protocol code numberESR-19-20262
    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 SponsorSahlgrenska University Hospital
    B.1.3.4CountrySweden
    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 supportAstraZeneca
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSahlgrenska University Hospital
    B.5.2Functional name of contact pointMichael Fu
    B.5.3 Address:
    B.5.3.1Street AddressDiagnosvägen 11
    B.5.3.2Town/ cityGothenburg
    B.5.3.4CountrySweden
    B.5.6E-mailMichael.fu@vgregion.se
    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 Yes
    D.2.1.1.1Trade name Lokelma
    D.2.1.1.2Name of the Marketing Authorisation holderAstrazeneca
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    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 namelokelma
    D.3.2Product code V03AE10
    D.3.4Pharmaceutical form Powder and solvent for oral suspension
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 placeboPowder for oral suspension
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Heart failure
    E.1.1.1Medical condition in easily understood language
    Heart failure is a serious condition, it means that the heart isn’t pumping as well as it should be and it requires seeking timely medical attention
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing MRA in symptomatic patients with heart failure
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    For inclusion in the study subjects should fulfil the following criteria:
    1. Obtain signed informed consent prior to any study specific procedures
    2. >18 yrs, irrespective of sex
    3. LVEF ≤ 40%, with echocardiography within last 2 years
    4. NYHA II-IV
    5. Stable heart failure as judged by local Investigator. Patients may be enrolled as an outpatient or in-hospital at, or close to, the time of hospital discharge
    6. On optimal treatment with GDMT (Guideline-Directed Medical Treatment including ACE/ARB/ARNI and beta blockers) as per physician´s judgement
    7. AND one of followings:
    (1) Prior hyperkalemia due to MRA therapy and current S-K ≤ 5.0 mmol/L;
    (2) Risk of hyperkalemia as indicated by eGFR 30-45 ml/min/1.73m2 and S-K 4.5-5.0 mmol/L;
    (3) Mild hyperkalemia (S-K 5.1-5.5 mmol/L) and MRA below target dose (target doses for spironolactone: 25-50 mg daily, and for eplerenone: 50 mg daily)
    E.4Principal exclusion criteria
    Subjects should not enter the study if any of the following exclusion criteria are ful-filled:
    1. Symptomatic hypotension (< 90/60 mmHg)
    2. eGFR < 30 ‎ml/min/1,73 m2 (modified MDRD formula)
    3. HF due to restrictive cardiomyopathy, hypertrophic (obstructive) cardiomy-opathy or primary valvular disease
    4. Current/recent (within 3 months) hospitalization due to myocardial infarc-tion, unstable angina pectoris, coronary revascularization (percutaneous cor-onary intervention or coronary artery bypass grafting), or other interventions (valvular repair/replacement, cardiac transplantation or implantation of a ven-tricular assistance device)
    5. Ongoing or planned dialysis
    6. Prior history of hypersensitivity (other than hyperkalemia) to a MRA, or SZC
    7. Advanced malignancy requiring treatment
    8. History of QT prolongation associated with other medications that required discontinuation of that medication.
    9. Congenital long QT syndrome.
    10. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymp-tomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
    11. QTc(f) > 550 msec
    12. Currently pregnant (confirmed with positive pregnancy test) or planned pregnancy or breast-feeding
    13. Can not sign informed consent.
    E.5 End points
    E.5.1Primary end point(s)
    To demonstrate the efficacy of Sodium Zir-conium Cyclosilicate (SZC) on optimizing MRA in heart failure, SZC vs Placebo.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at the end of study
    E.5.2Secondary end point(s)
    1.To determine the efficacy of SZC when com-pared to placebo in maintaining achieved MRA-dose after run-in period, SZC vs Placebo;

    2.To determine the impact of MRA-optimization by SZC in QoL-parameters, SZC vs Placebo;

    3.To determine the estimated treatment persisten-cy of highest tolerable dose (25-50 mg daily) of MRA, SZC vs Placebo;

    4. To evaluate the safety and tolerability of SZC when compared to placebo as assessed by differ-ences in percent (%) between the two groups in pre-specified safety endpoints (occurring at any point during the study)
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the end of study

    and throughtout the study for safety endpoint
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 concerned5
    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 No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 130
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state230
    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)
    To restore the original dose of minerocorticoid receptor antagonist (MRA) until dose before Run-in i.e returning the subject to their baseline (Run-in) MRA dose;

    Above procedure is carried out by a physical visit consisting of following steps
    1) Information about detailed planning of continuous follow-up after the end of study
    2) Information that investigator will send referral to patient´s ordinarie physi-cian/Clinic/Outpatient Clinic for continuous follow-up

    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-01-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-01-14
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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