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    Summary
    EudraCT Number:2017-000327-27
    Sponsor's Protocol Code Number:ISIS396443-CS2
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2017-01-26
    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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2017-000327-27
    A.3Full title of the trial
    An Open-Label, Dose Escalation Study to Assess the Safety, Tolerability and Dose-Range Finding of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Spinal Muscular Atrophy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open-Label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy
    A.4.1Sponsor's protocol code numberISIS396443-CS2
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/251/2016
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorIonis 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 supportIonis Pharmaceuticals
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBiogen
    B.5.2Functional name of contact pointBiogen Study Medical Director
    B.5.3 Address:
    B.5.3.1Street Address225 Binney Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post code02142
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@biogen.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/3/12/976
    D.3 Description of the IMP
    D.3.1Product nameSurvival of Motor Neuron 2 (SMN2) Splicing Modulator Antisense Oligonucleotide
    D.3.2Product code ISIS 396443
    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 INNnusinersen
    D.3.9.1CAS number 1258984-36-9
    D.3.9.3Other descriptive nameISIS 396443
    D.3.9.4EV Substance CodeSUB130563
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.4
    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 type2`-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
    Spinal Muscular Atrophy (SMA)
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy (SMA)
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To test the safety and tolerability of escalating doses of nusinersen (ISIS 396443) in participants with spinal muscular atrophy (SMA)
    E.2.2Secondary objectives of the trial
    To test the pharmacokinetics of escalating doses of nusinersen (ISIS 396443) in participants with spinal muscular atrophy (SMA)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Males and Females 2-15 years of age
    -Genetic documentation of 5qSMA (homozygous gene deletion or mutation)
    -Clinical signs attributable to SMA
    -Able to complete all study procedures, measurements, and visits and parent/patient has adequately supportive psychological circumstances, in the opinion of the investigator
    -Estimated life expectancy >2 years from Screening
    -Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedure
    E.4Principal exclusion criteria
    -Respiratory insufficiency defined by the medical necessity for invasive or non-invasive ventilation during a 24-hour period
    -Medical necessity for a gastric feeding tube, where the majority of feeds are given by this route, as assessed by the Investigator
    -Previous scoliosis surgery that would interfere with the lumbar puncture injection procedure
    -Hospitalization for surgery (e.g. scoliosis surgery) or pulmonary event within 2 months of screening or planned during the duration of the study
    -Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period
    -History of brain or spinal cord disease that would interfere with lumbar puncture procedures or cerebrospinal fluid (CSF) circulation
    -Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
    -History of bacterial meningitis
    -Dosing with ISIS 396443 in clinical study ISIS 396443-CS1 Cohorts 2, 3, or 4
    -Dosing with ISIS 396443 in clinical study ISIS 396443-CS10
    -Clinically significant abnormalities in hematology or clinical chemistry parameters or ECG at the Screening visit, as assessed by the Site Investigator that would render the subject unsuitable for inclusion
    -Treatment with investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Treatment with valproate or hydroxyurea within 3-months of screening. Any history of gene therapy or cell transplantation
    -Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, sever anemia) that would interfere with the assessment of safety or would compromise the ability of the patient to undergo study procedures
    E.5 End points
    E.5.1Primary end point(s)
    Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Highest Severity of AEs
    E.5.1.1Timepoint(s) of evaluation of this end point
    Duration of the study
    E.5.2Secondary end point(s)
    Plasma Pharmacokinetics, Cerebrospinal Fluid (CSF) Pharmacokinetics, Urine Pharmacokinetics
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 1, Day 29, Day 85
    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 Yes
    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.8.2.4Number of treatment arms in the trial4
    E.8.3 Will this trial be conducted at a single site globally? No
    E.8.4 Will this trial be conducted at multiple sites globally? Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.2Trial being conducted completely outside of the EEA Yes
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 34
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 25
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 9
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    For very young children, parents or legal representation consent will be requested
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 34
    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)
    Patients may be offered the opportunity to continue to receive ISIS 396443. This may occur via early access, extension of the treatment period, enrollment in another open label extension study. Patients may continue to receive treatment via one of these mechanisms until ONE of the following is met: ISIS 396443 is commercially available or is rejected in the local country. Sponsor terminates access to ISIS 396443 for reasons including safety issues or emergent data.
    G. Investigator Networks to be involved in the Trial
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: United States
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