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    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   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).

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    Summary
    EudraCT Number:2018-004670-10
    Sponsor's Protocol Code Number:AG10-333
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-05-25
    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 number2018-004670-10
    A.3Full title of the trial
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects with Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Trial)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of the Efficacy and Safety of AG10 in participants with Transthyretin Amyloid Polyneuropathy (ATTR-PN)
    A.3.2Name or abbreviated title of the trial where available
    Efficacy and Safety of AG10 in participants with Transthyretin Amyloid Polyneuropathy (ATTR-PN)
    A.4.1Sponsor's protocol code numberAG10-333
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1251-3220
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/330/2018
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorEidos 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 supportEidos Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEidos Therapeutics, Inc
    B.5.2Functional name of contact pointSr. Director, Clinical Operations
    B.5.3 Address:
    B.5.3.1Street Address101 Montgomery Street, Suite 2000
    B.5.3.2Town/ citySan Francisco
    B.5.3.3Post codeCA 94104
    B.5.3.4CountryUnited States
    B.5.4Telephone number001 415-651-3853
    B.5.6E-mailmmcgovern@eidostx.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 Yes
    D.2.5.1Orphan drug designation numberEMA/OD/096/18
    D.3 Description of the IMP
    D.3.1Product nameAG10
    D.3.2Product code AG10 HCl
    D.3.4Pharmaceutical form Film-coated 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 INNAG10 HCl
    D.3.9.1CAS number 2242751
    D.3.9.3Other descriptive name3-(3-(3,5-DIMETHYL-1H-PYRAZOL-4-YL)PROPOXY)-4-FLUOROBENZOIC ACID
    D.3.9.4EV Substance CodeSUB193376
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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 placeboFilm-coated tablet
    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
    Symptomatic Transthyretin Amyloid Polineuropathy (ATTR-PN)
    E.1.1.1Medical condition in easily understood language
    Symptomatic Transthyretin Amyloid Polineuropathy (ATTR-PN) is a rare disease that occurs when a protein, called transthyretin, is accumulated in the peripheral nerves.
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the efficacy of AG10 in the treatment of subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN) by evaluating the difference between the AG10 and placebo groups in Modified Neuropathy Impairment Score + 7 (mNIS+7) at 18 months of treatment relative to baseline
    E.2.2Secondary objectives of the trial
    Key secondary:
    To evaluate the effects of AG10 on:
    Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN), modified body mass index (mBMI), and Composite Autonomic Score (COMPASS-31) in subjects with symptomatic ATTR-PN
    Other Secondary:
    •To describe the pharmacodynamic (PD) properties of AG10 as assessed by serial measurements of an established assay of transthyretin (TTR) stabilization
    • To assess the pharmacodynamic effects of AG10 as assessed by circulating prealbumin (TTR) concentration as an in vivo biomarker of stabilization
    • To evaluate the effect of AG10 on health-related quality of life (QOL) and clinical outcome score as assessed by the Dyck/Rankin Score
    • To assess the effect of AG10 on gait speed as a reflection of functional ability
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Be able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures;
    2. Be male or female ≥18 to ≤90 years of age;
    3. Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIa) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical exam findings and/or neurophysiological test findings consistent with the diagnosis of ATTR-PN;
    4. Have an NIS of 5 to 130 (inclusive) during screening;
    5. Have a nerve conduction studies (NCS) score [sum of the sural sensory nerve action potential (SNAP), tibial compound muscle action potential (CMAP), ulnar SNAP, ulnar CMAP, and peroneal CMAP] of ≥2 points during screening. NCS is a component of mNIS+7;
    6. Have a mutation consistent with ATTR-PN either documented in medical history or confirmed by genotyping obtained at Screening prior to randomization. *No genetic testing is needed for subjects who are recipients of domino liver transplants;
    7. Have an anticipated survival of ≥2 years, in the opinion of the Investigator;
    8. Have Karnofsky performance status ≥60 %;
    9. Have serum albumin levels >3.0 g/dL;
    10. Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use a highly effective method of contraception beginning with randomization and continuing for 30 days after the last dose of AG10. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control. Postmenopausal state female subjects must be confirmed with plasma follicle-stimulating hormone (FSH) at Screening.
    E.4Principal exclusion criteria
    1. Had a prior liver transplantation or is planning to undergo liver transplantation with a wild-type organ graft as treatment for symptomatic ATTR-PN during the study period. Note: Recipients of a “domino” liver transplant from an ATTR-PN donor who have developed ATTR-PN mediated by their graft are allowed under this protocol, as long as re-transplantation to treat ATTR-PN is not planned during the study period and meets all other eligibility criteria;
    2. Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example, autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
    3. Has Vitamin B-12 levels below the lower limit of normal (LLN);
    4. Has clinical evidence of untreated hyper/hypothyroidism;
    5. Has leptomeningeal TTR amyloidosis;
    6. Has Type 1 diabetes;
    7. Has had Type 2 diabetes for ≥5 years;
    8. Has active hepatitis B or C or known human immunodeficiency virus (HIV) infection;
    9. Has NYHA heart failure classification >Class II;
    10. Had acute coronary syndrome, uncontrolled cardiac arrhythmia, or a stroke within 90 days prior to Screening;
    11. Has estimated glomerular filtration rate (eGFR) by Modification of Diet for Renal Disease (MDRD) formula <30 mL/min/1.73 m2 at Screening;
    12. Has abnormal liver function tests at Screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >3 × ULN;
    13. Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated;
    14. Has known hypersensitivity to Investigational Medicinal Product (IMP) (AG10 or placebo), its metabolites, or formulation excipients;
    15. Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or other gene silencing agents, marketed drug products lacking a label indication for ATTR-PN (e.g., diflunisal, doxycycline), natural products or derivatives used as unproven therapies for ATTR-PN (e.g., green tea extract, tauroursodeoxycholic acid [TUDCA]/ursodiol), within 14 days, or 90 days for patisiran and 180 days for inotersen prior to dosing. Prior to screening, tafamidis, if already prescribed to potential subjects as part of their established background therapy, is allowed at the labeled dosage and administration of 20 mg/day for the treatment of ATTR-PN with, in the opinion of the Investigator, evidence of disease progression while on tafamidis treatment;
    16. Female subjects who are pregnant or breastfeeding. Breastfeeding females must agree to discontinue nursing before IMP is administered. A negative urine pregnancy test at Screening and on Day 1 prior to randomization are required for female subjects of childbearing potential;
    17. In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or other condition that might jeopardize the subject’s safety, increase their risk from participation, or interfere with the study;
    18. Participation in another investigational drug or investigational device study within 30 days prior to dosing or 5 half-lives of the investigational drug, whichever is longer, with potential residual effects that might confound the results of this study;
    19. Has any condition that, in the opinion of the Investigator or Medical Monitor, would preclude compliance with the study protocol such as a history of substance abuse, alcoholism, or a psychiatric condition.
    E.5 End points
    E.5.1Primary end point(s)
    change from baseline to Month 18 in mNIS+7 score
    E.5.1.1Timepoint(s) of evaluation of this end point
    baseline, month 9 and month 18
    E.5.2Secondary end point(s)
    1.Change from baseline to Month 18 in Norfolk QOL-DN,
    2.Change from baseline to Month 18 in mBMI,
    3.Change from baseline to Month 18 in prealbumin levels
    4.Change from baseline to Month 18 in COMPASS-31
    5.Change from baseline to Month 18 of treatment in PD endpoints using established assay of TTR stabilization including Fluorescent Probe Exclusion (FPE) assay.
    6.Change from baseline to Month 18 of treatment in Dyck/Rankin score at each assessed time point.
    7.Change from baseline to Month 18 of treatment in gait speed.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Baseline, 9 and 18 months
    2. Baseline, 9 and 18 months
    3. Baseline, 3, 6, 9, 13, 15 and 18 months
    4. Baseline, 9 and 18 months
    5. Baseline, 9 and 18 months
    6. Baseline, 9 and 18 months
    7. Baseline, 9 and 18 months
    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 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 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 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Brazil
    Bulgaria
    Canada
    France
    Germany
    Hungary
    Italy
    Mexico
    Netherlands
    New Zealand
    Poland
    Portugal
    Russian Federation
    Spain
    Taiwan
    Turkey
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days12
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months7
    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: 87
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 58
    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 state11
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 145
    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)
    All subjects who complete the double-blinded treatment period may be eligible to participate in an open label extension study of long-term AG10 treatment
    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 Decision2020-09-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-08-20
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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