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    Summary
    EudraCT Number:2017-002471-25
    Sponsor's Protocol Code Number:BN40697(ISIS443139-CS2)
    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:2017-08-07
    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 ConcernedGermany - BfArM
    A.2EudraCT number2017-002471-25
    A.3Full title of the trial
    An Open-Label Extension Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7234292 (ISIS 443139) in Huntington’s Disease Patients Who Participated in Prior Investigational Studies of RO7234292 (ISIS 443139)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An extension study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the study drug, RO7234292 (ISIS 443139), in patients who participated in prior investigational studies of RO7234292
    A.4.1Sponsor's protocol code numberBN40697(ISIS443139-CS2)
    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 SponsorF.Hoffmann La-Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF.Hoffmann La-Roche Ltd - Basel
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche LTD
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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/3/15/1453
    D.3 Description of the IMP
    D.3.2Product code Ro 723-4292/F02
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrathecal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNn.a.
    D.3.9.1CAS number 1709886-74-7
    D.3.9.2Current sponsor codeRO7234292
    D.3.9.3Other descriptive nameRG6042, formerly ISIS 443139, IONIS-HTTRx
    D.3.9.4EV Substance CodeSUB173711
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 type2ʹ-MOE Antisense Oligonucleotide
    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
    Early Manifest Huntington's Disease
    E.1.1.1Medical condition in easily understood language
    Early Manifest Huntington's Disease
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10070668
    E.1.2Term Huntington's disease
    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 monthly and bimonthly (every other month) intrathecal (IT) bolus administrations of RO7234292 to patients with Huntington's disease (HD).
    E.2.2Secondary objectives of the trial
    To characterize the cerebrospinal fluid (CSF) pharmacokinetics of monthly and bimonthly IT doses of RO7234292.
    To explore effects of monthly and bimonthly IT doses of RO7234292 on key pharmacodynamic biomarkers and clinical endpoints relevant to HD, including:
     - Mutant huntingtin protein (mutant Htt) level in CSF
     - Structural MRI (ventricular, caudate and whole brain volumes)
    - Quantitative electroencephalography
     - Assessments of physical functioning, activities of daily living, gait, balance, mobility, and cognitive functioning
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Must be capable of giving informed consent (in the opinion of the Investigator)
    2. Must have completed the Treatment Period of Study ISIS 443139-CS1
    3. Able and willing to meet all study requirements in the opinion of the Investigator,
    4. Females must be non-pregnant, non-lactating
    E.4Principal exclusion criteria
    1. Treatment with an investigational drug (other than ISIS 443139 in Study ISIS 443139-CS1), biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer. Concurrent or planned concurrent participation in any clinical study (including observational and non-interventional studies) without approval of the Sponsor Medical Monitor
    2. Antiplatelet or anticoagulant therapy within the 14 days prior to first lumbar puncture in the study or anticipated use during the study, including but not limited to aspirin (unless ≤ 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban
    3. Prior treatment with an antisense oligonucleotide including siRNA (other than ISIS 443139 in Study ISIS 443139-CS1)
    4. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
    5. Clinically-relevant hematological, hepatic, cardiac or renal disease or event. Clinically-significant abnormal hepatic, renal or hematology lab
    tests at Screening must be discussed with the Sponsor MedicalMonitor
    6. Malignancy within 5 years of Screening, except for basal or squamouscell carcinoma of the skin or carcinoma in situ of the cervix that has
    been successfully treated
    7. Any condition that significantly increases risk of meningitis unlesspatient is receiving appropriate prophylactic treatment
    8. History of bleeding diathesis or coagulopathy, platelet count < LLN unless stable and assessed by the Investigator and Sponsor Medical Monitor to be not clinically significant
    9. Have any other condition which, in the opinion of the Investigator or Sponsor, would make the patient unsuitable for inclusion or could
    interfere with the patient participating in or completing the study
    E.5 End points
    E.5.1Primary end point(s)
    There is no single primary endpoint for this study. Important endpoints that will be evaluated are listed below:
    Safety and Tolerability Endpoints
     - Columbia - Suicide Severity Rating Scale (C-SSRS)
     - Physical examination and standard neurological assessment (including fundi)
     - Pregnancy testing
    - Vital signs (heart rate [HR], BP, orthostatic changes, weight)
     - ECG
     - AEs and concomitant medications
     - CSF safety labs (cell counts, protein, glucose)
     - Plasma laboratory tests (clinical chemistry, hematology)
     - Urinalysis
     -Safety neuroimaging assessments
    .
    E.5.1.1Timepoint(s) of evaluation of this end point
    Continuous
    E.5.2Secondary end point(s)
    Pharmacokinetic Endpoints
    Plasma C max, AUC, elimination half-life and trough and post-distribution drug levels will be assessed, where appropriate. CSF elimination half-life and trough drug levels will be assessed, where appropriate. Urinary excretion parameters such as amount of drug excreted and renal clearance will be determined, as appropriate. Biochemical Endpoints:
    Mutant huntingtin protein (mutant Htt) level in CSF. Neuroimaging Endpoints: Structural MRI (ventricular, caudate and whole brain volumes). Electrophysiological Endpoints:
    Quantitative electroencephalography. Clinical Endpoints: Assessments of physical functioning, activities of daily living, gait, balance, mobility, and cognitive functioning
    E.5.2.1Timepoint(s) of evaluation of this end point
    CSF is collected periodically during the study (prior to each RO7234292 dose and once each during screening and follow-up). Imaging, EEG and cognitive data are collected approximately every 6 months. Functional data, such as gait and ADL, are collected throughout the study using handheld devices.
    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 No
    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 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 No
    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 EEA8
    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
    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 years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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: 43
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 3
    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 state19
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 46
    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 completing study treatment in Study BN40697, the patients will be eligible to enroll in another OLE study (BN40955) with active RO7234292 compound, provided the data from the ongoing RO7234292 program Support continued development, the Patient meets the inclusion and exclusion criteria for the OLE, and the OLE meetsapproval by the relevant competent authorities, IRBs, and ECs.
    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 Decision2017-12-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-10
    P. End of Trial
    P.End of Trial StatusCompleted
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