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   43861   clinical trials with a EudraCT protocol, of which   7284   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:2020-002997-28
    Sponsor's Protocol Code Number:ISIS304801-CS20
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2021-01-16
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2020-002997-28
    A.3Full title of the trial
    An Open-Label Study of Volanesorsen (ISIS 304801) Administered
    Subcutaneously to Pediatric Patients with Familial Chylomicronemia
    Syndrome (FCS)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of the drug Volanesorsen (ISIS 304801) in children and adolescent patients with Familial Chylomicronemia Syndrome (FCS)
    A.4.1Sponsor's protocol code numberISIS304801-CS20
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/185/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAkcea Therapeutics, 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 supportAkcea Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAkcea Therapeutics, Inc.
    B.5.2Functional name of contact pointAkcea Clinical Trials
    B.5.3 Address:
    B.5.3.1Street Address22 Boston Wharf Road, 9th Floor
    B.5.3.2Town/ cityBoston
    B.5.3.3Post codeMA02210
    B.5.3.4CountryUnited States
    B.5.6E-mailakceaclinicaltrials_304801CS20@akceatx.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 Yes
    D.2.1.1.1Trade name WAYLIVRA®
    D.2.1.1.2Name of the Marketing Authorisation holderAkcea Therapeutics Ireland Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/3/14/1249
    D.3 Description of the IMP
    D.3.1Product nameVolanesorsen
    D.3.2Product code ISIS 304801
    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 INNVolanesorsen
    D.3.9.2Current sponsor codeISIS 304801
    D.3.9.4EV Substance CodeSUB187365
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Familial Chylomicronemia
    Syndrome
    E.1.1.1Medical condition in easily understood language
    An inherited disease that prevents the body from breaking down fats
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10020606
    E.1.2Term Hyperchylomicronaemia
    E.1.2System Organ Class 10027433 - Metabolism and nutrition 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 volanesorsen sodium (ISIS 304801) administered by subcutaneous (SC)
    injection to adolescent and pediatric patients with FCS.
    E.2.2Secondary objectives of the trial
    To evaluate the safety, pharmacodynamic profile, and pharmacokinetic profile of volanesorsen sodium
    (ISIS 304801) administered by subcutaneous (SC) injection to adolescent and pediatric patients with
    FCS.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Cohort 1 Inclusion Criteria:
    1. Age ≥ 12 years and < 18 years at time of informed consent and assent, as required by regional laws or regulations
    Cohort 2 Inclusion Criteria:
    1. Age ≥ 2 years to < 12 years at time of informed consent and assent, as required by regional laws or regulations
    Cohort 1 and 2 Inclusion Criteria:
    2. Written informed consent/assent and any authorizations required by law must be obtained from the patient and parent(s) (or legally authorized representative) after the nature of the study has been explained and before any assessment is performed
    3. Confirmed homozygote, compound heterozygote or double heterozygote for known loss-of-function mutations in FCS-causing genes (such as LPL, APOC2, APOA5, LMF1 or GP1HBP1)
    4. Fasting TG ≥ 880 mg/dL (~10 mmol/L) at screening. If the fasting TG is < 880 mg/dL, up to two additional tests may be performed in order to qualify
    5. Willing to follow a diet for optimal control of TGs and disease management during the study

    For patients of reproductive age, an additional inclusion criterion:
    6. Satisfy one of the following:
    a. Females: Non-pregnant and non-lactating; abstinent*, or if engaged in sexual relations of childbearing potential, patient agrees to use an acceptable contraceptive method (refer to Section 6.3.1) from time of signing the informed consent/assent form until 13 weeks after the last visit in the Treatment Period
    b. Males: Abstinent* or if engaged in sexual relations with a female of childbearing potential, patient is utilizing an acceptable contraceptive method (refer to Section 6.3.1) from the time of signing the informed consent/assent form until 13 weeks after the last visit in the Treatment Period

    * Abstinence (i.e. refraining from heterosexual intercourse) is only acceptable to meet the contraception requirements of the study if it is true abstinence. This means that abstinence must be the preferred and usual lifestyle of the patient. Periodic abstinence (i.e. calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and/or withdrawal are not acceptable methods of
    contraception
    E.4Principal exclusion criteria
    1. Body weight < 10 kg
    2. Type 1 or Type 2 diabetes mellitus
    3. Any of the following laboratory values at screening
    a. Hepatic:
    • Total bilirubin > upper limit of normal (ULN), unless prior diagnosis and documentation of
    Gilbert’s syndrome in which case total bilirubin must be ≤ 3 mg/dL
    • Alanine Aminotransferase (ALT) > 2.0 x ULN
    • Aspartate Aminotransferase (AST) > 2.0 x ULN
    b. Renal:
    • Persistently positive proteinuria: urine protein/creatinine ratio (UPCR) > 0.2 mg/mg on 2 tests
    separated by at least 7 days
    • Persistently positive hematuria: urine microscopy showing > 5 red blood cells per high power field
    on 2 tests separated by at least 7 days
    • Estimated GFR (eGFR) < 75 mL/min/1.73m2 using the Bedside Schwartz formula (Selistre 2016)
    c. Low density lipoprotein-cholesterol (LDL-C) > 130 mg/dL at screening
    d. Platelet count < 140,000/mm3
    e. Any other laboratory abnormalities which, in the opinion of the Investigator or the Sponsor, would
    make the patient unsuitable for inclusion
    4. History of chronic kidney disease
    5. Uncontrolled thyroid disease
    6. Has uncontrolled hypertension (average clinic measured SBP and/or DBP ≥95th percentile on the basis of
    age, sex, and height percentiles)**
    **See Appendix E Blood Pressure Tables for Boys and Girls by Age and Height Percentile
    7. History of bleeding diathesis or coagulopathy or clinically-significant abnormality in coagulation parameters
    at screening
    8. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to
    Study Day 1
    9. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis
    B
    10. History of malignancy
    11. History of alcoholism or drug/chemical abuse within 1 year of screening
    12. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer
    13. Unwilling or unable to comply with lifestyle requirements
    14. History of major psychosis or major depressive disorder
    15. Use of any of the following:
    a. Statins, omega-3 fatty acids (prescription and over-the-counter [OTC]), or fibrates unless on a stable dose for at least 3 months prior to screening and dose and regimen expected to remain constant during the Treatment Period. Patients taking OTC omega-3 fatty acids should make every effort to remain on the same brand throughout the study
    b. Nicotinic acid or derivatives of nicotinic acid within 4 weeks prior to screening
    c. Systemic corticosteroids or anabolic steroids within 6 weeks prior to screening
    d. Treatment with oral anticoagulant medications
    e. Estrogens or progestins (including birth control pills) unless on a stable dose for at least 6 weeks prior to screening and dose and regimen expected to remain constant during the Treatment Period
    f. Plasma apheresis within 4 weeks prior to screening or planned during the study
    g. Prior exposure to volanesorsen within the last 6 months
    h. Any other medication unless stable at least 4 weeks prior to screening. Occasional or intermittent use of over-the-counter medications will be allowed at Investigator’s discretion
    16. Known hypersensitivity to any of the excipients of volanesorsen
    17. In the opinion of the Investigator, inability to comply with the protocol
    18. Have any other conditions, including history of significant cardiac disease which, in the opinion of the Investigator or the Sponsor would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study
    E.5 End points
    E.5.1Primary end point(s)
    To evaluate the efficacy of volanesorsen administered SC to adolescent and pediatric patients with Familial Chylomicronemia Syndrome (FCS) by assessing the following:
    • Percent change in fasting triglycerides from Baseline to the primary analysis time point at Week 13.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline, Week 13
    E.5.2Secondary end point(s)
    To further evaluate the efficacy, safety and PK/PD profile of volanesorsen administered SC to adolescent and pediatric patients with Familial Chylomicronemia Syndrome (FCS) by assessing the following:
    • Percent change from baseline in fasting TG at Weeks 25, 53, 77, and 105
    • Change from baseline in fasting TG at Weeks 13, 25, 53, 77, and 105
    • Proportion of patients who achieve fasting TG < 750 mg/dL overall and at Weeks 13, 25, 53, 77, and 105
    • Proportion of patients who achieve fasting TG < 500 mg/dL overall and at Weeks 13, 25, 53, 77, and 105
    • Proportion of patients who achieve ≥ 40% fasting TG reduction from baseline overall and at Weeks 13, 25, 53, 77, and 105
    • Change and percent change from baseline in other fasting lipid measurements at Weeks 13, 25, 53, 77, and 105 including: total apolipoprotein C-III (apoC-III), total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein-cholesterol (HDL-C), apoB, apoA-1,
    very-low-density lipoprotein-cholesterol (VLDL-C), and low-density lipoprotein-cholesterol (LDLC)
    • Comparison of adjudicated acute pancreatitis event rate and patient reported abdominal pain prior to first dose of Study Drug (including events based on medical chart review) vs. adjudicated pancreatitis events and patient reported abdominal pain on treatment at Week 25 and Week 53
    • Change from baseline in hepatosplenomegaly as assessed by MRI at Week 53 and optional Week 105
    • Change in Quality of Life from baseline at Weeks 13, 25, 53, 77, and 105
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline, 13, 25, 53, 77, and 105
    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 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 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 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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
    Australia
    Serbia
    South Africa
    Austria
    France
    Germany
    Italy
    Netherlands
    Poland
    Spain
    Switzerland
    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
    last patient, last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 16
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 8
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 8
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 14
    F.4.2.2In the whole clinical trial 16
    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)
    Standard of care
    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 Decision2021-01-04
    N.Ethics Committee Opinion of the trial applicationWithdrawn
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-03-17
    P. End of Trial
    P.End of Trial Status
    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-Fri Apr 26 06:48:08 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA