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   43871   clinical trials with a EudraCT protocol, of which   7290   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:2011-001483-21
    Sponsor's Protocol Code Number:KBT009
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2011-05-24
    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 ConcernedAustria - BASG
    A.2EudraCT number2011-001483-21
    A.3Full title of the trial
    A Placebo-controlled, Double-blind, Randomised, Parallel-group, Long-term Phase III Trial Assessing the Safety and Efficacy of 50 µg and 100 µg/day of eprotirome in Patients with Heterozygous Familial Hypercholesterolaemia who are on Optimal Standard of Care
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study on patients suffering from high level cholesterols. The aim is to evaluate safety and efficacy of a new medicinal drug.
    A.3.2Name or abbreviated title of the trial where available
    AKKA
    A.4.1Sponsor's protocol code numberKBT009
    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 SponsorKaro Bio AB
    B.1.3.4CountrySweden
    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 supportKaro Bio
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKaro Bio AB
    B.5.2Functional name of contact pointRegulatory Affairs Director
    B.5.3 Address:
    B.5.3.1Street AddressNovum, Halsovagen 7
    B.5.3.2Town/ cityHuddinge
    B.5.3.3Post codeSE-141 57
    B.5.3.4CountrySweden
    B.5.4Telephone number+468 608 6007
    B.5.5Fax number+468608 6188
    B.5.6E-mailelisabeth.augustsson@karobio.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 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 nameeprotirome
    D.3.2Product code KB2115
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNeprotirome
    D.3.9.1CAS number CAS355129-15
    D.3.9.2Current sponsor codeKB2115
    D.3.9.3Other descriptive nameBMS356384
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    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 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 placeboTablet
    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
    Heterozygous Familial Hypercholesterolaemia
    E.1.1.1Medical condition in easily understood language
    high levels of cholesterol
    E.1.1.2Therapeutic area Body processes [G] - Metabolic Phenomena [G03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level LLT
    E.1.2Classification code 10057099
    E.1.2Term Heterozygous familial hypercholesterolaemia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    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 of this study is to compare the efficacy of eprotirome 50 µg and eprotirome 100 µg versus placebo in terms of the percent change in LDL-C from baseline to Week 12 in HeFH patients with CAD, or who are at high risk for CAD, and who are on optimal standard of care consisting of a statin with or without ezetimibe
    E.2.2Secondary objectives of the trial
    •To compare the efficacy of eprotirome 50µg and 100 µg versus placebo in terms of the percent change in LDL-C from baseline to Week 28, 52, 76, and 100;in TG, HDL C, non-HDL-C, TC, (apo) A-I, apo B, Lp[a], and markers for inflammation (eg, hsCRP) from baseline to Week 12, 28, 52, 76, and 100;
    •To compare the efficacy of eprotirome 50 µg and 100 µg versus placebo in terms of the proportion of patients who have a reduction in LDL-C of >15% from baseline to Week 12;
    •To monitor the systemic exposure to the nitrated reaction product KB42899 in the population through sparse sampling and explore the pharmacokinetics (PK) of KB42899 and eprotirome through rich sampling in selected cases;
    •Evaluation for knee-joint function and symptoms using a PRO questionnaire, KOOS
    •Long term safety and tolerability of eprotirome
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    1) DXA Scan and Echocardiography
    In subsets of patients, safety assessments will also include echocardiography and DXA scans of the lumbar spine for BMD. The DXA scan substudy will be composed of the first 300 patients who qualify and are able to undergo a screening/baseline DXA scan (ie, no presence of osteoporosis and no orthopaedic hardware in the lumbar region). The echocardiogram substudy will be composed of the first 300 patients who qualify and undergo a screening/baseline echocardiogram. This substudy is included in the main protocol.
    2) Holter Monitoring
    Holter monitors will be used to assess cardiac activity over a 24-hour time period. The Holter monitoring substudy will enroll 30 patients. This substudy is included in the main protocol.
    E.3Principal inclusion criteria
    1)Patients with confirmed HeFH who are 18 years of age or older, understand the study procedures and agree to participate in the study by giving written informed consent at Visit 1 and must have:
    a) Presence of clinical atherosclerotic disease that confers high risk for CAD events together with an LDL-C >2 mmol/L (>80 mg/dL) at Visit 2, based on one or more of the following; or
    b) Presence of at least 2 risk factors for CVD (other than the HeFH diagnosis) together with an LDL-C >2.5 mmol/L (>100 mg/dL) at Visit 2:
    2) Patients should be on an optimal standard of care, defined as being on a stable dose of statin (at least half of the maximum dose of either rosuvastatin, atorvastatin, or simvastatin) with or without ezetimibe for at least 8 weeks prior to randomisation. If lower doses of rosuvastatin, atorvastatin, or simvastatin or any dose of fluvastatin or pravastatin are used the reasons must be clearly documented.
    3) Women must not be pregnant or lactating. Women of childbearing potential must use a medically acceptable form of contraception at least 4 weeks prior to the start of the study and for at least 4 weeks after the patient’s last study visit. Subjects who are on systemic hormonal contraceptives must agree to use an additional method of contraception (barrier method).
    4) Diabetes mellitus (Type 1 and Type 2), for Type 2 (only metformin, sulfonylureas, alpha-glucosidase inhibitors or DPP-4s as antidiabetic medications are allowed)
    E.4Principal exclusion criteria
    1) Other dyslipidaemic or metabolic disorders that could affect the evaluation of eprotirome in HeFH, such as increased serum TG >4.5 mmol/L, HbA1c >8.5%, secondary dyslipidaemia or ongoing or planned apharesis
    2) cardiac diseases that may interfere with the safety evaluation of eprotirome, such as congestive heart failure (NYHA III and IV), planned percutaneous coronary intervention, coronary
    artery bypass surgery, unstable angina pectoris, myocardial infarction, uncontrolled hypertension (defined as systolic blood pressure equal to or more than 160 mmHg or diastolic blood pressure equal to or more than 100 mmHg) or evidence of cardiac electrophysiologic instability including uncontrolled sick sinus syndrome, sino-atrial or atrioventricular block, ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardia with a ventricular response heart rate (>100 bpm) or a QTcF >450 ms
    3) Previous stroke (includes definite or presumed cerebral ischaemia/infarction)
    4) No other lipid-lowering medication with the exception of statins and ezetimibe are allowed
    5) Patients with disturbed thyroid function, thyrotoxicosis, taking thyroid hormone or anti-thyroid medication are excluded
    6) Drugs known to affect thyroid function tests are also prohibited
    7) Patients with liver dysfunction such as: AST or ALT or ALP >1.5 x ULN, total bilirubin >ULN, active hepatobiliary disease, cholestasis, or serologic evidence of past or active hepatitis B or hepatitis C, acquired immune deficiency syndrome, positive HIV, substantial consumption of alcohol or drug abuse
    8) Patients with serum creatinine >160 mmol/L or unexplained serum creatine kinase >3 x ULN
    9) Patients on oral anticoagulant therapy other than vitamin K antagonists and anti-platelets agents
    10) Rheumatoid arthritis; history of cancer, history of or current primary or secondary adrenal insufficiency or any other condition that in the opinion of the investigator confound the evaluation and interpretation of efficacy and or safety data.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy:
    The percent change in LDL-C from baseline to Week 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    E.5.2Secondary end point(s)
    Efficacy:
    Percent change in LDL-C from baseline to Week 28, Week 52, Week 76, and Week 100;
    Percent change in TG, HDL-C, non-HDL-C, TC, apo A-I, apo B, Lp(a), and hsCRP from baseline to Week 12, Week 28, Week 52, Week 76, and Week 100; and
    Proportion of patients with an LDL-C reduction from baseline of more than 15% at Week 12.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12, Week 28, Week 52, Week 76 and Week 100
    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 Yes
    E.6.10Pharmacogenetic Yes
    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 trial3
    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 EEA41
    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
    Austria
    Czech Republic
    Denmark
    India
    Israel
    Netherlands
    Norway
    Russian Federation
    South Africa
    Spain
    Sweden
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    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: 1050
    F.1.3Elderly (>=65 years) Yes
    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 state113
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 626
    F.4.2.2In the whole clinical trial 1050
    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)
    No treatment planned.
    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 Decision2011-07-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-06-20
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2012-02-24
    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-Sat May 04 15:04:10 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA