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    Summary
    EudraCT Number:2014-001229-34
    Sponsor's Protocol Code Number:ALN-TTRSC-003
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-10-03
    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 ConcernedUK - MHRA
    A.2EudraCT number2014-001229-34
    A.3Full title of the trial
    A Phase 2, Open-label Extension Study to Evaluate the Long-Term Safety, Clinical Activity, and Pharmacokinetics of ALN-TTRSC in Patients with Transthyretin (TTR) Cardiac Amyloidosis Who Have Previously Received ALN-TTRSC
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The Phase 2 Open-Label Extension Study of an Investigational Drug, ALN-TTRSC, in Patients with TTR Cardiac Amyloidosis
    A.4.1Sponsor's protocol code numberALN-TTRSC-003
    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 SponsorAlnylam 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 supportAlnylam Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace, UK
    B.5.2Functional name of contact pointFaisal Zaman, Clinical Trial Mngr.
    B.5.3 Address:
    B.5.3.1Street AddressKingfisher House, Elmfield Road
    B.5.3.2Town/ cityBromley
    B.5.3.3Post codeBR1 1LT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number44208315-6786
    B.5.5Fax number44208315-6793
    B.5.6E-mailf.zaman@medpace.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 numberEU/3/14/1267 (EMA/OD/194/13)
    D.3 Description of the IMP
    D.3.1Product nameALN-TTRSC
    D.3.2Product code ALN-TTRSC
    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 INNrevusiran
    D.3.9.2Current sponsor codeALN-51547
    D.3.9.3Other descriptive nameALN-51547
    D.3.9.4EV Substance CodeSUB104164
    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
    Transthyretin (TTR) Cardiac Amyloidosis
    E.1.1.1Medical condition in easily understood language
    ATTR is a hereditary disease caused by protein aggregates in the heart and the nervous system. It leads to heart dysfunction, damages to the nerves, and gastrointestinal and bladder dysfunctions
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level SOC
    E.1.2Classification code 10010331
    E.1.2Term Congenital, familial and genetic disorders
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic 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 safety and tolerability of long-term dosing with ALN-TTRSC
    E.2.2Secondary objectives of the trial
    To assess the PD effect of long-term dosing of ALN-TTRSC on serum levels of TTR.
    To assess the clinical effects of long-term dosing of ALN-TTRSC, including effect on mortality, hospitalization, and 6-MWT.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Previously received and tolerated ALN-TTRSC in Study ALN-TTRSC-002; and completed Study ALN-TTRSC-002 through the Day 90 visit

    2. Adequate liver function, demonstrated by an aspartate transaminase and alanine transaminase ≤ 2.5 × the upper limit of normal, total bilirubin< 2 g/dL (34.2 μmol/L), and albumin > 3 g/dL (> 4.35 μmol/L)

    3. Women of child-bearing potential (WOCBP) must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception prior to Screening/Baseline, throughout study participation, and for 1 month after last dose administration

    4. Males who agree to use appropriate means of contraception throughout study participation until 1 month after last dose administration

    5. Patient, or patient’s legal representative, is able and willing to provide written informed consent and the patient is willing to comply with the study requirements.
    E.4Principal exclusion criteria
    1. Estimated Glomerular Filtration Rate < 20 mL/min/1.73m2 (using the Modification of Diet in Renal Disease [MDRD] formula)

    2. Uncontrolled hypertension

    3. Uncontrolled ischemic heart disease

    4. Uncontrolled clinically significant cardiac arrhythmia

    5. Untreated hypo- or hyperthyroidism

    6. Prior major organ transplant

    7. Known or suspected systemic bacterial, viral, parasitic, or fungal infection

    8. Seropositive for hepatitis B virus, hepatitis C virus (HCV) or known to be human immunodeficiency virus positive

    9. Received an investigational agent other than tafamidis, diflunisal, doxycycline, or tauroursodeoxycholic acid, or an investigational device within 30 days prior to first dose of study drug

    10. Discontinued ALN-TTRSC-002 study due to a treatment-related AE

    11. Metastatic cancer within the past 5 years

    12. Any conditions which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the patient’s participation in, or completion of, the study

    13. History of allergic reaction to an oligonucleotide or GalNAc
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability of long-term dosing of ALN-TTRSC, including:
    • Assessment of AEs
    • Clinical laboratory safety tests (hematology, serum chemistry including liver function tests [LFTs], thyroid function, coagulation, and urinalysis)
    • Vital sign measurements (blood pressure, pulse rate, oral body temperature, and respiratory rate)
    • 12-Lead ECG
    • Physical examinations
    • Eye examinations
    E.5.1.1Timepoint(s) of evaluation of this end point
    • AEs will be collected throughout the study.
    • Safety evaluations will be performed as part of Screening and approximately every 12 weeks during the treatment period with the exception of eye examinations, which will be performed once a year
    E.5.2Secondary end point(s)
    • To assess the PD effect of long-term dosing of ALN-TTRSC on serum levels of TTR.
    • To assess the clinical effects of long-term dosing of ALN-TTRSC, including effect on mortality, hospitalization, and 6-MWT

    E.5.2.1Timepoint(s) of evaluation of this end point
    • Pharmacodynamic (PD) evaluation will include serial measurement of serum levels of TTR at specified time points. Serum levels of vitamin A will also be evaluated as a secondary PD biomarker.
    • Evaluations of clinical efficacy will be performed as part of Screening and approximately every 24 weeks during the treatment period

    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) 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 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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    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
    United Kingdom
    United States
    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 years4
    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 years4
    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: 3
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 22
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 25
    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)
    Consistent with pre-study treatment, if any.
    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 Decision2014-08-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-07-18
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-02-22
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