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   43801   clinical trials with a EudraCT protocol, of which   7258   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:2021-001427-40
    Sponsor's Protocol Code Number:ION-682884-CS13
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-01-28
    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 number2021-001427-40
    A.3Full title of the trial
    An Open-Label, Extension Study to Assess the Long-Term Safety and Efficacy of ION-682884 in Patients with Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to Assess the Long-Term Safety and Efficacy of ION-682884 in Patients with Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
    A.4.1Sponsor's protocol code numberION-682884-CS13
    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 SponsorIonis 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 supportIonis Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIonis Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointIonis Clinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address2855 Gazelle Court
    B.5.3.2Town/ cityCarlsbad
    B.5.3.3Post codeCA 92010
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1760 931 9200
    B.5.5Fax number+1760 603 2504
    B.5.6E-mailClinicalTrials@ionisph.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameION-682884
    D.3.2Product code ION-682884
    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 INNEplontersen
    D.3.9.1CAS number 1637600-16-8
    D.3.9.2Current sponsor codeION-682884
    D.3.9.3Other descriptive nameION-682884
    D.3.9.4EV Substance CodeSUB199528
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 Yes
    D.3.11.13.1Other medicinal product typeAntisense Oligonucleotide
    D.IMP: 2
    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 nameION-682884
    D.3.2Product code ION-682884
    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 INNEplontersen
    D.3.9.1CAS number 1637600-16-8
    D.3.9.2Current sponsor codeION-682884
    D.3.9.3Other descriptive nameION-682884
    D.3.9.4EV Substance CodeSUB199528
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number56
    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 Yes
    D.3.11.13.1Other medicinal product typeAntisense Oligonucleotide
    D.IMP: 3
    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 nameION-682884
    D.3.2Product code ION-682884
    D.3.4Pharmaceutical form Solution for injection in pre-filled injector
    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 INNEplontersen
    D.3.9.1CAS number 1637600-16-8
    D.3.9.2Current sponsor codeION-682884
    D.3.9.3Other descriptive nameION-682884
    D.3.9.4EV Substance CodeSUB199528
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number56
    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 Yes
    D.3.11.13.1Other medicinal product typeAntisense Oligonucleotide
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
    E.1.1.1Medical condition in easily understood language
    An inherited condition that causes damage to peripheral nerves
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10057949
    E.1.2Term Familial amyloid polyneuropathy
    E.1.2System Organ Class 100000004850
    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 is to evaluate the safety and tolerability of extended dosing with ION-682884 (eplontersen) in patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN).
    E.2.2Secondary objectives of the trial
    The secondary objective is to evaluate the efficacy of extended dosing with ION-682884.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Satisfactory completion of ION-682884-CS3 as judged by the Investigator and Sponsor, OR diagnosis of hATTR-PN and satisfactory completion of study ISIS 420915-CS101 (an Investigator-Sponsored study with inotersen - the unconjugated version of ION-682884) as judged by the Investigator and Sponsor
    2. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
    3. Satisfy the following:
    a. Females: must be non-pregnant and non-lactating and either:
    − Surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy)
    − Post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved)
    − Abstinent*or
    − If engaged in sexual relations of child-bearing potential, agree to use highly effective contraceptive methods (Section 6.4.1) from the time of signing the informed consent form until at least 24 weeks after the last dose of ION-682884 and agree to receive pregnancy tests per protocol
    b. Males: Surgically sterile (i.e., bilateral orchidectomy) or abstinent*, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the patient’s non-pregnant female partner must use a highly effective contraceptive method (Section 6.4.1) from the time of signing the informed consent form until at least 24 weeks after the last dose of ION-682884 *Abstinence (i.e., refraining from heterosexual intercourse throughout the duration of study participation) is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.
    4. Willingness to adhere to vitamin A supplementation per protocol
    E.4Principal exclusion criteria
    1. Have any new condition or worsening of existing condition that in the opinion of the Investigator or Sponsor would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoints (PEP) are change from Baseline (Index Study Baseline and separately
    open-label extension [OLE] Baseline) in the following measures:
    • Platelet count, renal function and transaminases
    • Adverse events (AE)
    • Use of concomitant medications
    • Vital signs and weight
    • Physical examination findings
    • Clinical laboratory tests
    • Electrocardiogram (ECG) parameters
    • Thyroid panel tests
    • Coagulation tests
    • Inflammatory panel tests
    • Complement and immunogenicity tests
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoints (PEP) are change from Baseline (Index Study Baseline and separately
    open-label extension [OLE] Baseline) in the following measures:
    • Platelet count and renal function
    • Adverse events (AE)
    • Use of concomitant medications
    • Vital signs and weight
    • Physical examination findings
    • Clinical laboratory tests
    • Electrocardiogram (ECG) parameters
    • Thyroid panel tests
    • Coagulation tests
    • Inflammatory panel tests
    • Complement and immunogenicity tests
    E.5.2Secondary end point(s)
    The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE
    Baseline) in the following measures:
    • Neuropathy Impairment Score (NIS)
    • Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire
    • Neuropathy Symptom and Change score (NSC)
    • Serum Transthyretin (TTR) concentration
    • Physical Component Summary score (PCS) of 36-Item Short Form Survey (SF-36)
    • Polyneuropathy disability score (PND)
    • Modified body mass index (mBMI)
    • Composite Autonomic Symptom Score-31 (COMPASS-31)
    • 5 Level EQ-5D (EQ-5D-5L)
    E.5.2.1Timepoint(s) of evaluation of this end point
    The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE
    Baseline) in the following measures:
    • Neuropathy Impairment Score (NIS)
    • Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire
    • Neuropathy Symptom and Change score (NSC)
    • Serum Transthyretin (TTR) concentration
    • Physical Component Summary score (PCS) of 36-Item Short Form Survey (SF-36)
    • Polyneuropathy disability score (PND)
    • Modified body mass index (mBMI)
    • Composite Autonomic Symptom Score-31 (COMPASS-31)
    • 5 Level EQ-5D (EQ-5D-5L)
    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 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA13
    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
    Brazil
    Canada
    New Zealand
    Taiwan
    United States
    Cyprus
    France
    Sweden
    Spain
    Germany
    Italy
    Portugal
    Turkey
    E.8.7Trial has a data monitoring committee No
    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
    The End-of-Study is last patient, last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days8
    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: 116
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 52
    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 state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 53
    F.4.2.2In the whole clinical trial 165
    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 completing the Treatment Period, patients will enter a 24-week Post-treatment Evaluation Period that consists of clinic and non-clinic visits. If a patient discontinues treatment in this study, but is continuing to receive treatment with ION-682884 via another mechanism, the entry of the patient into the 24-week Post-treatment Evaluation Period may be omitted.
    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 Decision2022-03-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-04-26
    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA