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:2015-004003-23
    Sponsor's Protocol Code Number:ISIS703802
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-05-27
    Trial results View 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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-004003-23
    A.3Full title of the trial
    A Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ISIS 703802, Targeting ANGPTL3, Administered Subcutaneously to Healthy Volunteers with Elevated Triglycerides and
    Subjects with Familial Hypercholesterolemia
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A controlled study to assess the safety, tolerability and activity of the study drug ISIS 703802 given subcutaneously to Healthy Volunteers with high triglycerides and patients with Familial Hypercholesterolemia
    A.4.1Sponsor's protocol code numberISIS703802
    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 pointTeresa Brandt
    B.5.3 Address:
    B.5.3.1Street Address2855 Gazelle Ct.
    B.5.3.2Town/ cityCarlsbad, CA
    B.5.3.3Post code92010
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1760603-2738
    B.5.5Fax number+1760603-3891
    B.5.6E-mailtbrandt@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 nameISIS 703802
    D.3.2Product code ISIS 703802
    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 INNISIS 703802
    D.3.9.2Current sponsor codeISIS 703802
    D.3.9.3Other descriptive nameISIS 703802
    D.3.9.4EV Substance CodeSUB180375
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 type2′-MOE Chimeric Antisense Oligonucleotide
    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
    Heterozygous familial hypercholesterolemia and Homozygous familial hypercholesterolemia
    E.1.1.1Medical condition in easily understood language
    Hypercholesterolemia
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10054380
    E.1.2Term Familial hypercholesterolemia
    E.1.2System Organ Class 100000004850
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10057080
    E.1.2Term Homozygous familial hypercholesterolemia
    E.1.2System Organ Class 100000004850
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10057079
    E.1.2Term Heterozygous familial hypercholesterolemia
    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
    • To evaluate the safety and tolerability of single and multiple doses of ISIS 703802 administered subcutaneously to healthy subjects with elevated triglycerides (TG) and subjects with familial hypercholesterolemia.
    • To evaluate the pharmacokinetics (PK) of single and multiple SC doses of ISIS 703802 in healthy subjects with elevated TGs and in multiple-dose subjects with familial hypercholesterolemia.
    • To evaluate the effects of single and multiple SC doses of ISIS 703802 on pharmacodynamics in healthy subjects with elevated TG and in multiple-dose subjects with familial hypercholesterolemia, including: plasma angiopoietin-like 3 (ANGPTL3), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non HDL-C), very low density lipoprotein cholesterol (VLDL-C), and TG.
    • To explore the effects of multiple SC doses of ISIS 703802 on post-heparin lipoprotein lipase (LPL) and TG.
    E.2.2Secondary objectives of the trial
    Not Applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria for All Cohorts:
    •Must have given written informed consent and be able to comply with all study requirements
    •Males or females 18 to 65 years, inclusive, at the time of informed consent
    •BMI ≤ 35.0 kg/m2
    •Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal.
    •Males must be surgically sterile, abstinent or using an acceptable contraceptive method

    Inclusion Criteria for Cohort EE Only:
    •Homozygous FH diagnosis and fasting LDL-C ≥ 190 mg/dL (4.9 mmol/L)

    Inclusion Criteria for Cohort FF Only:
    •Heterozygous FH diagnosis and fasting LDL-C ≥ 160 mg/dL (4.1 mmol/L)

    Inclusion Criteria for Cohorts EE and FF Only:
    •Maximally tolerated stable LDL-C lowering agents (stable for at least 12 weeks)
    •On stable low-fat diet
    •Stable weight (± 4 kg) for ≥ 6 weeks prior to screening
    E.4Principal exclusion criteria
    Exclusion Criteria for All Cohorts:
    •Known history or positive test for HIV, HCV, or HBV
    •Treatment with another Study Drug, biological agent, or device within one-month or 5-half-lives of screening
    •Regular use of alcohol within 6 months of screening
    •Use of concomitant drugs unless authorized by the Sponsor Medical Monitor
    •Known contraindication and/or allergy to heparin
    •Smoking > 10 cigarettes a day
    •Considered unsuitable for inclusion by the Principal Investigator

    Exclusion Criteria for Cohorts EE and FF:
    •Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to screening, or cerebrovascular accident within 24 weeks prior to screening. Subjects with adequately treated stable angina, per Investigator assessment, may be included
    •Congestive heart failure defined by NYHA Classes III or IV
    •T2DM with HbA1c > 8.0%
    •Prior treatment with gene therapy
    •Currently receiving apheresis treatments or last apheresis treatment was within 8 weeks of screening
    E.5 End points
    E.5.1Primary end point(s)
    •Safety and tolerability of single and multiple doses of IONIS ANGPTL3-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
    The safety and tolerability of IONIS ANGPTL3-LRx will be assessed by determining the incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS ANGPTL3-LRx will be compared with those from subjects dosed with placebo.

    •Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx.
    The plasma pharmacokinetics (concentration-time results) of IONIS ANGPTL3-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of IONIS ANGPTL3-LRx excreted in urine at selected 24-hour intervals will also be determined.

    •Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels)
    Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    LPLV - Day 127
    E.5.2Secondary end point(s)
    Pharmacodynamic effects of IONIS ANGPTL3-LRx:
    Effects of IONIS ANGPTL3-LRx on changes in ANGPTL3 plasma protein compared to baseline.
    E.5.2.1Timepoint(s) of evaluation of this end point
    LPLV - Day 127
    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) Yes
    E.7.1.1First administration to humans Yes
    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 No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Double blind and Open Label Cohorts
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    Canada
    Italy
    Netherlands
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days0
    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: 61
    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 Yes
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 7
    F.4.2.2In the whole clinical trial 61
    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 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 Decision2016-09-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-05-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-06-26
    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-Thu Apr 25 15:20:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA