Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-003153-28
    Sponsor's Protocol Code Number:ALN-TTRSC02-003
    National Competent Authority:Croatia - MIZ
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-11-12
    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 ConcernedCroatia - MIZ
    A.2EudraCT number2019-003153-28
    A.3Full title of the trial
    HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)
    HELIOS-B: randomizirano, dvostruko slijepo, placebom kontrolirano, multicentrično ispitivanje 3. faze za procjenu učinkovitosti i sigurnosti vutirisirana u ispitanika s transtiretinskom amiloidozom s kardiomiopatijom (ATTR-amiloidoza s kardiomiopatijom)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy
    A.3.2Name or abbreviated title of the trial where available
    Helios B
    A.4.1Sponsor's protocol code numberALN-TTRSC02-003
    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 SponsorAlnylam Pharmaceuticals, Inc.
    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 supportAlnylam Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAlnylam Pharmaceuticals, Inc
    B.5.2Functional name of contact pointClinical Trials Information Line
    B.5.3 Address:
    B.5.3.1Street Address300 Third Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post code02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number+ 001877256 9526
    B.5.6E-mailclinicaltrials@alnylam.com
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2026
    D.3 Description of the IMP
    D.3.1Product namevutrisiran
    D.3.2Product code ALN-TTRSC02
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    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 INNvutrisiran
    D.3.9.1CAS number 1867157-35-4
    D.3.9.2Current sponsor codeALN-65492
    D.3.9.3Other descriptive nameALN-65492
    D.3.9.4EV Substance CodeSUB182382
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Yes
    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 in pre-filled syringe
    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
    Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)
    E.1.1.1Medical condition in easily understood language
    Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)
    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 PT
    E.1.2Classification code 10007509
    E.1.2Term Cardiac amyloidosis
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of vutrisiran compared to placebo on reducing all-cause mortality and Cardiovascular (CV) events
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of vutrisiran compared with placebo treatment on:
    - Functional capacity
    - Patient-reported health status and healthrelated quality of life
    - Cardiac structure and function
    - Additional assessments of death, hospitalizations, and urgent heart failure (HF) visits
    - Components of the primary composite outcome endpoint (all-cause mortality, and CV events)
    - Cardiac biomarkers
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18 (or age of legal consent per local regulations, whichever is older) to 85 years, inclusive.
    2. Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy
    3. Medical history of HF with at least 1 prior hospitalization for HF (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker) OR clinical evidence of HF (with or without hospitalization) manifested by signs and symptoms of volume overload or elevated intracardiac pressures (eg, elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that currently requires treatment with a diuretic.
    4. Patient meets one of the following criteria:
    a. Tafamidis-naïve and not actively planning to commence treatment with tafamidis during the first 12 months following randomization (per exclusion criterion #7); or
    b. On tafamidis (Note: must be on-label use of commercial tafamidis per an approved cardiomyopathy indication and dose in the country of use)
    5. Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization, as assessed by the Investigator.
    6. Screening NT-proBNP >300 ng/L and <8500 ng/L; in patients with permanent or persistent atrial fibrillation, Screening NT-proBNP >600 ng/L and <8500 ng/L..
    7. Able to complete ≥150 meters on the 6-MWT at Screening.
    8. Have a Karnofsky performance status of ≥60%.
    9. Patient is able to understand and is willing and able to comply with the study requirements and to provide written informed consent.
    10. Patient agrees to sign a separate medical records release form, where allowed by local regulations, to allow for the collection of information on vital status, cardiac transplant procedures, left-ventricular assist device placement, and hospitalizations, for the duration of the DB Period of the study.
    E.4Principal exclusion criteria
    1. Has known primary amyloidosis(AL amyloidosis)or leptomeningeal amyloidosis
    2. NYHA Class IV heart failure; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP >3000 ng/L and eGFR <45 ml/min)
    3. Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk due to polyneuropathy, or is wheelchair bound) at the Screening visit
    4. Has any of the following laboratory parameter assessments at Screening: a. AST or ALT levels >2.0 × ULN; b. Total bilirubin >2.0 × ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible if the total bilirubin is <2 × ULN); c. International normalized ratio (INR) >1.5 (unless patients were on anticoagulant therapy in which case excluded if INR >3.5)
    5. Has eGFR <30 mL/min/1.73 m2 (using the modification of diet in renal disease [MDRD] formula) at Screening
    6. Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection
    7. Tafamidis-naïve patients (per inclusion criterion #4a) for whom the Investigator actively plans or anticipates commencing treatment with tafamidis either during the Screening Period or the first 12 months following randomization, taking into consideration clinical status, patient preference and/or commercial availability of tafamidis
    8. Received prior TTR-lowering treatment (including revusiran, patisiran or inotersen) or participated in a gene therapy trial for hATTR amyloidosis
    9. Currently taking diflunisal; if previously on this agent, must have at least a 30-day wash-out prior to dosing (Day 1)
    10. Currently taking doxycycline, ursodeoxycholic acid or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 30-day wash-out prior to dosing (Day 1)
    11. Unwilling to avoid any concurrent treatment with diflunisal, ursodeoxycholic acid/tauroursodeoxycholate/doxycycline, or TTR lowering agents (eg, patisiran, inotersen)
    12. Current or future participation in another investigational device or drug study, scheduled to occur during this study, or has received an investigational agent or device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline (inclusion criterion #4)
    13. Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem)
    14. Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzymes and ECG changes) that the Investigator feels is a significant contributor or the predominant cause of the patient’s heart failure
    15. Unstable congestive heart failure (CHF) (including patients who require adjustment of existing diuretics or addition of new diuretics at time of Screening for purposes of achieving optimal management of CHF)
    16. Had acute coronary syndrome or unstable angina within the past 3 months
    17. Has history of sustained ventricular tachycardia or aborted ventricular fibrillation
    18. Has history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker is indicated but will not be placed
    19. Has persistent elevation of systolic (>170 mmHg) or diastolic (>100 mmHg) blood pressure that is considered uncontrolled by physician
    20. Has untreated hypo- or hyperthyroidism
    21. Has an active infection requiring systemic antiviral, antiparasitic or antimicrobial therapy that will not be completed prior to dosing (Day 1)
    22. Prior or anticipated (during the first 12 months after randomization) heart, liver or other organ transplant or implantation of left-ventricular assist device
    23. History of multiple drug allergies; or history of allergic reaction to any component of or excipient in the study drug
    24. History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability
    25. Has other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
    26. Is not willing to comply with the contraceptive requirements during the study period
    27. Female patient is pregnant, planning a pregnancy, or breast-feeding
    28. Unwilling or unable to limit alcohol consumption throughout the course of the study
    29. History of alcohol abuse, within the last 12 months before Screening, in the opinion of the Investigator
    30.History of illicit drug abuse within the past 5 years that in the opinion of the Investigator would interfere
    E.5 End points
    E.5.1Primary end point(s)
    Composite outcome of all-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits)
    E.5.1.1Timepoint(s) of evaluation of this end point
    36 months
    E.5.2Secondary end point(s)
    - Change from baseline in 6-minute walk test (6-MWT)

    - Change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS)

    - Change from baseline in mean left ventricular (LV) wall thickness (by echocardiographic assessment)

    - Change from baseline in global longitudinal strain (by echocardiographic assessment)

    - Composite endpoint of all-cause mortality and recurrent all-cause hospitalizations and urgent HF visits.

    - All-cause mortality

    - Recurrent CV events (CV hospitalizations and urgent HF visits)

    - Change from baseline in N-terminal prohormone B-type natriuretic peptide (NT-proBNP)
    E.5.2.1Timepoint(s) of evaluation of this end point
    6-MWT: Weeks 1, 24, 48, 72, 84, 108, 132
    KCCQ-OS: Weeks 1, 24, 48, 72, 84, 108, 132
    echocardiogram: Weeks 48, 72, 108, 132
    NT-proBNP: Weeks 12, 24, 36, 48, 72, 108, 132
    mortality and CV events assessed over 36 month 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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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 trial1
    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 concerned39
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA39
    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
    Argentina
    Australia
    Canada
    Israel
    Japan
    Jordan
    Korea, Republic of
    Peru
    United States
    Austria
    France
    Lithuania
    Poland
    Sweden
    Netherlands
    Spain
    Czechia
    Germany
    Belgium
    Croatia
    Denmark
    Hungary
    Ireland
    Norway
    Portugal
    United Kingdom
    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
    Posljednji posjet posljednjeg uključenog ispitanika
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    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: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 300
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 600
    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)
    After participation in the trial has ended, patients will be treated at the discretion of their physician based on local standard of care. In the case where there are no commercially available treatment options, the Sponsor will aim to provide access to vutrisiran via the means available
    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 Decision2020-06-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-02-27
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 07 08:51:50 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA