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:2014-003107-29
    Sponsor's Protocol Code Number:N°005
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-01-28
    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 ConcernedGermany - BfArM
    A.2EudraCT number2014-003107-29
    A.3Full title of the trial
    A Phase IIb, double blind, randomized controlled clinical trial to evaluate the efficacy and safety of two Aramchol doses versus placebo in patients with Non-Alcoholic- Steatohepatitis (NASH).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase IIb, double blind, randomized controlled clinical trial to evaluate the efficacy and safety of two Aramchol doses versus placebo in patients with Non-Alcoholic- Steatohepatitis (NASH).
    A.4.1Sponsor's protocol code numberN°005
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02279524
    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 SponsorGALMED Pharmaceuticals LTD.
    B.1.3.4CountryIsrael
    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 supportGALMED Pharmaceuticals LTD.
    B.4.2CountryIsrael
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGALMED Pharmaceuticals LTD.
    B.5.2Functional name of contact pointEphry Gilad
    B.5.3 Address:
    B.5.3.1Street Address16 Ze’ev Tiomkin St.
    B.5.3.2Town/ cityTel Aviv
    B.5.3.3Post code6578317
    B.5.3.4CountryIsrael
    B.5.4Telephone number97236938448
    B.5.5Fax number97236938447
    B.5.6E-mailephry@galmedgroup.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 nameAramchol
    D.3.2Product code Aramchol
    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 INNAramchol
    D.3.9.1CAS number 246529-22-6
    D.3.9.3Other descriptive nameAramchol
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number200 to 400
    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
    Non-alcoholic Steatohepatitis in patients with two additional features of metabolic syndrome -overweight or obesity and Diabetes Mellitus type II or pre-diabetes.
    E.1.1.1Medical condition in easily understood language
    Fatty liver associated to inflammation and lesions.
    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 10053219
    E.1.2Term Non-alcoholic steatohepatitis
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    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 efficacy on steatosis reduction as measured by NMRS of two Aramchol doses (400 mg and 600 mg), once daily for 52 weeks vs placebo.
    E.2.2Secondary objectives of the trial
    1. To evaluate the efficacy of Aramchol on CRN Fibrosis Score by liver biopsy.
    2. To evaluate the efficacy of Aramchol on disease activity as measured by NAS and SAF activity score
    3. To evaluate the efficacy of Aramchol on NASH resolution by liver biopsy.
    4. To evaluate the effect of Aramchol on ALT levels.
    Exploratory objectives:
    1. To evaluate the effect of Aramchol on metabolic parameters.
    2. To compare two doses in order to choose the optimal dose for pivotal Phase III studies.
    3. To assess Aramchol’s effect on NASH activity by non-invasive diagnostic methods.
    4. To validate new non-invasive tests for the diagnostic and assessments of Aramchol’s effect.
    5. To conduct blood trough level of Aramchol.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Genetic sub-study about correlation between response to Aramchol treatment and PNPLA3 genotype.
    E.3Principal inclusion criteria
    1. Male or female age 18 to 75 years.
    2. BMI between 25kg/m2 to 40kg/m2 or waist circumference between 88cm to 200cm for women, and between 102cm to 200cm for men. If there is deviation above the upper limit, please consult the MRI center, to ensure that the machine is suitable for the patient
    3. Known type II Diabetes Mellitus or pre-Diabetes according to American Diabetes Association. One of the following 3 criteria is needed for pre-Diabetes: Fasting Plasma Glucose > 100mg/dl (5.5mmol/l) or 2hPG following 75g OGTT > 140 (7.8 mmol/l) mg/dl or HbA1c > 5.7%. HbA1c can be repeated at Investigator’s discretion
    4. Histologically proven Steatohepatitis on a diagnostic liver biopsy performed either during Screening , or within 6 months before screening visit, confirmed by central laboratory reading of the slides (steatosis ≥1 + inflammation ≥1 + ballooning ≥1). Total activity NAS score of 4 or more.
    5. Liver fat concentration of 5.5% or more as measured by NMRS.
    6. Biopsies with an activity NAS score of 4 or more.
    7. Normal synthetic liver function (serum albumin >3.2g/dl, INR 0.8-1.2, conjugated bilirubin < 35 μmol/L).
    8. Understanding the nature of the study and signature of the written informed consent.
    9. Negative pregnancy test at study entry for females of child bearing potential.
    10. Females of child bearing potential practicing reliable contraception throughout the study period (including oral contraceptives). If barrier methods are used, it is recommended to practice two methods (e.g. male condom + female diaphragm with spermicide). For country-specific requirements (e.g. Germany) contraception failure rates (Pearl Index) should be under 1% in accordance with the recommendations of the CTFG Working Group on Contraception.
    11. Hypertensive patients must be well controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening.
    12. Patients previously treated with vitamin E (>400IU/day), Polyunsaturated fatty acid (>2g/day), Ursodeoxycholic acid or fish oil can be included if drugs are stopped at least 3 months prior to diagnostic liver biopsy (and are not started during the trial). These treatments-dosages are allowed if they were stable for at least 12 months prior to biopsy and can remain stable throughout the study. (Dosages less than the amounts stated above are allowed without washout- or stable-period restrictions).
    13. For patients with type II Diabetes, glycaemia must be controlled (Glycosylated Hemoglobin A1c ≤ 9% while any HbA1c change should not exceed 1.5% during the 6 months prior to enrollment). Treatments with anti-diabetic medications (except for those mentioned in Exclusion 16) are permitted if glycaemia is self-monitored by the patient. HbA1c can be repeated at Investigator’s discretion.
    E.4Principal exclusion criteria
    1. Patients with other active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, unless eradicated at least 3 years prior to screening; genetic hemochromatosis; Wilson disease; alpha 1antitripsin deficiency; alcohol liver disease, drug induced liver disease) at the time of randomization.
    2. Patients with clinically or histologically documented liver cirrhosis (CRN fibrosis score =4).
    3. Known alcohol and/or any other drug abuse or dependence in the last five years.
    4. Known history or presence of clinically significant cardiovascular, hepatic other than NASH, gastrointestinal, metabolic other than Diabetes Mellitus, neurologic, pulmonary, endocrine, psychiatric,neoplastic disorder or nephrotic syndrome, that in the opinion of the Investigator warrant exclusion from the study.
    5. Patients with familial (i.e., genetic) hypertriglyceridemia and familial (i.e., genetic) hypercholesterolemia.
    6. History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including bile salt metabolism (e.g. inflammatory bowel disease (IBD); previous intestinal (ileal or colonic) operation; chronic pancreatic; celiac disease or previous vagotomy. Ongoing chronic constipation.
    7. Patients with heart or brain pacemaker. (i.e., implantable neurological devices).
    8. Surgery within three months of screening which involved stent implantation of metal devices (e.g., knee, hip etc.)
    9. Weight loss of more than 5% within 6 months prior to randomization.
    10. History of bariatric surgery within 5 years of liver biopsy.
    11. Uncontrolled arterial hypertension.
    12. Women who are pregnant or breast feeding.
    13. Diabetes Mellitus other than type II (type I, endocrinopathy, genetic syndromes etc.).
    14. Patients with HIV infection.
    15. Daily alcohol intake >20 g/day for women and >30 g/day for men (on average per day), as per medical history.
    16. Treatment with other anti-diabetic medications: GLP-1 receptor agonists and Thiazolidinediones (TZDs) unless started at least 12 months prior to biopsy and on stable dose over 6 months. In case GLP-1 receptor agonist being stopped, it should be at least 6 months prior to biopsy, as per medical history.
    17. SGLT-2 Inhibitors, Metformin, fibrates, statins, insulin, DPP-4 inhibitors and sulfonylurea unless the prescribed dose has been stable for the last 6 months prior to the biopsy.
    18. Treatment with Valproic acid, Tamoxifen, Methotraxete, Amiodarone or chronic treatment with anti-cholinergic agents, corticosteroids, high dose estrogen and tetracycline within 12 months prior to the screening visit.
    19. Chronic antibiotic treatment (e.g. Rifaximin).
    20. Homeopathic and/or alternative treatments. Any treatment should be stopped during the screening period, at least 48 hours before randomization.
    21. Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone >2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
    22. Patients with renal dysfunction eGFR< 40.
    23. Unexplained serum creatine phosphokinase (CPK) >3X the upper limit of normal (ULN). Patients with an intermittent CPK elevation may have the repeated measurement prior to randomization; a CPK retest > 3X ULN leads to exclusion.
    24. Patients with condition(s) that makes them unsuitable to perform the NMRS (as determined by the PI or the MRI facility).
    25. Known Hypersensitivity to Aramchol or to any of the excipients in the tablets
    26. Known Hypersensitivity to cholic acid or bile acid sequestrants
    E.5 End points
    E.5.1Primary end point(s)
    Percent (%) change from baseline to end of study in liver triglycerides ratio as measured by NMRS.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At screening and at week 52
    E.5.2Secondary end point(s)
    1. Proportion (%) of subjects with CRN fibrosis score improvement
    2. Proportion (%) of subjects with NAS score improvement without worsening of CRN fibrosis score.
    3. Proportion (%) of subjects with SAF activity score improvement without worsening of CRN Fibrosis Score.
    4. Proportion (%) of subjects with NASH resolution without worsening of CRN fibrosis score
    5. Change from baseline to Week 52/Termination in ALT (U/L) levels.
    Exploratory endpoints:
    1. Change from baseline to Week 52/Termination in HOMA-IR (UNITS).
    2. Change from baseline to Week 52/Termination in HEMOGLOBIN A1C (%).
    3. Change from baseline to Week 52/Termination in
    ADIOPONECITINE (TOTAL) (mg/L).
    4. Change from baseline to Week 52/Termination in LEPATIN (pg/mL) / ADIOPONECITINE (TOTAL) (mg/L) ratio (LAR)
    5. Change from baseline to Week 52/Termination in inflammation and fibrosis biomarkers: FIBRINOGEN (ACT) (g/L), CYTOKERATIN 18 (M-30) (U/L), CYTOKERATIN 18 (M-65) (U/L), hs-CRP (mg/L), HS-IL6 (ng/L), TNFa [HS-TNF A (ng/L)] and NAFLD fibrosis score (NFS).
    6. Change from baseline to Week 52/Termination in body weight and in waist circumference.
    7. Change from baseline to Week 52/Termination in fatty liver index (FLI).
    8. Endothelial function.
    9. Aramchol blood trough level.
    10. Metabolomics.
    11. Genetic profiling.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. At screening and at week 52.
    2. At screening and at week 52.
    3.At screening, baseline, visit 2, visit 7, visit 10, visit 11.
    4. At screening, week 24, week 52, and unscheduled visit.
    5. At screening, week 8, week 24, week 40, week 52, and unscheduled visit.
    6. At screening and at week 52.
    7. At screening and at week 52.
    8. At screening, baseline, week 24, week 52, week 65, and unscheduled visit.
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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) 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 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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
    Chile
    France
    Germany
    Israel
    Italy
    Mexico
    Peru
    Romania
    United States
    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 years2
    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 years2
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 130
    F.4.2.2In the whole clinical trial 240
    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 the treatment period (52 weeks) the patients will be controlled for a follow-up period of 13 weeks without administration of treatment. Since the patients included in this trial belong to the pool of the investigational sites where they are recruited, it is foreseen that they will continue the treatment for NASH according to the standard site clinical practice. At this stage the possibility of a care program after the study period has not been evaluated yet.
    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 Decision2015-08-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-04-23
    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-Mon May 06 21:58:16 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA