A Phase 1-3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION363 in Amyotrophic Lateral Sclerosis Patients With Fused in Sarcoma Mutations (FUS-ALS)

Study Purpose:

The primary purpose of this study is to evaluate the clinical efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations with amyotrophic lateral sclerosis (FUS-ALS).


Amyotrophic Lateral Sclerosis (ALS),  Familial ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:



Phase III

Study Chair(s)/Principal Investigator(s):

Clinicaltrials.gov ID (11 digit #):


Neals Affiliated?


Coordinating Center Contact Information

Ionis Pharmaceuticals / .(JavaScript must be enabled to view this email address) / 844-421-0104
.(JavaScript must be enabled to view this email address) United States

Full Study Summary:

This is a multi-center, two-part study of ION363 in up to 64 participants. Part 1 will consist of participants that will be randomized in a 2:1 ratio to receive a multi-dose regimen of ION363 or placebo for a period of 29 weeks, followed by Part 2, which will be an open-label period where all participants will receive ION363 for a period of 73 weeks.

Study Sponsor:

Ionis Pharmaceuticals, Inc.

Participant Duration:

Estimated Enrollment:


Estimated Study Start Date:


Estimated Study Completion Date:


Posting Last Modified Date:


Date Study Added to alsconsortium.org:

  • Eligibility Criteria


    Female, Male

    Minimum Age:


    Maximum Age:


    Min Vital Capacity (% predicted normal):


    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    Inclusion Criteria:

    1. Signs or symptoms consistent with an ALS disease process in the opinion of the Investigator
    2. Confirmed genetic mutation in FUS in a clinical laboratory improvement amendments (CLIA) certified testing laboratory and classified as "pathogenic" or "likely pathogenic". Mutations classified as "Variants of Unknown Significance" must be approved by a variant classification committee
    3. An Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) pre-study slope ≥ 0.4 prior to Screening if 30 to 65 years of age, inclusive, at the time of informed consent
    4. Upright (sitting position) slow vital capacity (SVC) as adjusted for sex, age, and height ≥ 50 percentage (%) of predicted value
    5. Participants taking edaravone must be on a stable dose for ≥ 28 days prior to Screening and riluzole must be on a stable dose for ≥ 28 days prior to Day 1, and willing to continue on that dose throughout the duration of the study, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study
    6. Stable concomitant medications and nutritional support for at least 1 month prior to Study Day 1. Concomitant medications or nutritional support that have not been stable for at least 1 month prior to Study Day 1 may be allowed in consultation with the Sponsor Medical Monitor or designee.
    7. Has an informant/caregiver who, in the Investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities at Screening. Participants < 18 years old at Screening must have a trial partner (parent, caregiver or other) who is reliable, competent and at least 18 years of age, is willing to accompany the participant to trial visits and to be available to the Study Center by phone if needed, and who (in the opinion of the Investigator) is and will remain sufficiently knowledgeable of participant's ongoing condition to respond to Study Center inquiries about the participant

    Exclusion Criteria:

    1. Requiring permanent ventilation (> 22 hours of mechanical ventilation [invasive or noninvasive] per day for > 21 consecutive days) and/or tracheostomy
    2. Any known ALS-associated mutations except FUS
    3. Positive test result indicating chronic or active hepatitis B or hepatitis C or human immunodeficiency virus (HIV), hepatitis C or hepatitis B diagnosed by initial serological testing and confirmed with RNA testing, or prior treatment for hepatitis C.
    4. Clinically significant (CS) abnormalities in medical history (e.g., previous acute coronary syndrome within 3 months of Screening, major surgery within 2 months of Screening) or physical examination, unless discussed and approved by the Sponsor Medical Monitor
    5. Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm Hg])
    6. Malignancy within 1 year of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Participants with a history of other malignancies that have been treated with curative intent and which have no recurrence within 6 months may also be eligible if approved by the Sponsor medical monitor
    7. Obstructive hydrocephalus
    8. Known significant brain or spinal disease that would interfere with the lumbar puncture (LP) process, CSF circulation or safety assessment, including tumors or abnormalities by magnetic resonance imaging (MRI) or computed tomography (CT), subarachnoid hemorrhage, suggestion of raised intracranial pressure on MRI or ophthalmic examination, spinal stenosis or curvature, chiari malformation, obstructive hydrocephalus, syringomyelia, tethered spinal cord syndrome and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome
    9. Concurrent participation in any other interventional clinical study
    10. Previous treatment with an oligonucleotide (including small interfering RNA [siRNA])
    11. Treatment with another investigational drug, biological agent, or device, including, but not limited to sodium phenylbutyrate, within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
    12. History of gene therapy or cell transplantation or any other experimental brain surgery
    13. Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with the individual participating in or completing the study

  • Site Contact Information

    Barrow Neurological Institute
    Phoenix, Arizona 85013
    United States

    University of California San Diego
    Rose Previte / .(JavaScript must be enabled to view this email address) / 617-697-4856
    La Jolla, California 92037
    United States

    Stanford University Medical Center
    .(JavaScript must be enabled to view this email address) / Palo Alto, California 94304
    United States

    Massachusetts General Hospital
    Gabriel Jacobs / .(JavaScript must be enabled to view this email address) / 617-726-3015
    Kush Mehta / .(JavaScript must be enabled to view this email address) / 617-643-5376
    Boston, Massachusetts 02114
    United States

    Washington University School of Medicine
    Kelly McCoy Gross / .(JavaScript must be enabled to view this email address) / 844-257-2273
    Saint Louis, Missouri 63110
    United States

    Columbia University Medical Center
    Sonya Aziz-Zaman / .(JavaScript must be enabled to view this email address) / 646-799-2175
    New York, New York 10032
    United States

    The Ohio State University Wexner Medical Center
    Alison Sankey / .(JavaScript must be enabled to view this email address) / 614-688-7812
    Columbus, Ohio 43210
    United States

    University of Utah
    Salt Lake City, Utah 84132
    United States

    UZ Leuven
    Philip van Damme / .(JavaScript must be enabled to view this email address) / +32 16 34 42 80

    Montreal Neurological Institute
    .(JavaScript must be enabled to view this email address) / Montreal, Quebec

    King's College Hospital
    Dr. Keith Mayl / .(JavaScript must be enabled to view this email address) / +44 7802598741
    United Kingdom