A Study to Evaluate the Efficacy Safety Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)

  • End date
    Mar 4, 2024
  • participants needed
  • sponsor
    Ionis Pharmaceuticals, Inc.
Updated on 4 October 2021
primary lateral sclerosis


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).


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 77 weeks.

Condition Myelopathy, Amyotrophic Lateral Sclerosis, Amyotrophic Lateral Sclerosis (ALS), Spinal Cord Disorders, lou gehrig's disease
Treatment Placebo, ION363
Clinical Study IdentifierNCT04768972
SponsorIonis Pharmaceuticals, Inc.
Last Modified on4 October 2021


Yes No Not Sure

Inclusion Criteria

Signs or symptoms consistent with an ALS disease process in the opinion of the Investigator
Participants in
Cohort A must be, at the time of informed consent, 12 - 65 years of age
inclusive, with signs or symptoms consistent with an ALS disease process in
the opinion of the Investigator and if 30 to 65 years of age, inclusive, have
an ALSFRS-R pre-study slope 0.4 points per month (calculated as [48-Screening
ALSFRS-R score]/time in months since symptom onset)
Cohort B must be, at the time of informed consent, > 30 years of age, with
signs or symptoms consistent with an ALS disease process in the opinion of the
Investigator and have an ALSFRS-R pre-study slope < 0.4 points per month
(calculated as [48-Screening ALSFRS-R score]/time in months since symptom
\. Confirmed genetic mutation in FUS in a clinical laboratory improvement
amendments (CLIA) certified, CE-marked, or equivalent testing laboratory and
classified as "pathogenic" or "likely pathogenic". Mutations not pre-approved
per the Variant Classification Manual must be reviewed and approved by a
variant classification committee
\. Upright (sitting position) slow vital capacity (SVC) as adjusted for sex
age, and height 50 percentage (%) of predicted value
\. 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
\. 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
\. 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
Inclusion Criteria for Part 2
Completed, or rescued from, Part 1, or
Enrolled and received at least 1 dose of ION363 in the Investigator-initiated EAP program
Patient meeting Criteria #1-2 is otherwise suitable for study participation, in the opinion of the Investigator

Exclusion Criteria

Requiring permanent ventilation (> 22 hours of mechanical ventilation [invasive or noninvasive] per day for > 21 consecutive days) and/or tracheostomy
Any known ALS-associated mutations except FUS
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
Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm Hg])
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
Obstructive hydrocephalus
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
Concurrent participation in any other interventional clinical study
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
History of gene therapy or cell transplantation or any other experimental brain surgery
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
Positive test result for
Human immunodeficiency virus (HIV)
Hepatitis C (HCV), unless previously treated and has been serum/plasma HCV RNA negative for at least 6 months after the end of treatment
Hepatitis B (HBV) by HBV surface antigen test, unless currently on nucleotide/nucleoside analogue treatment
Previous treatment with an oligonucleotide (including small interfering RNA [siRNA]). This exclusion criterion does not apply to COVID-19 vaccinations, which are allowed
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note