Summary

Eligibility
for people ages 12-65 (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

Summary

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).

Official Title

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)

Details

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.

Keywords

Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations Sarcoma Mutations Sarcoma Motor Neuron Disease Sclerosis ION363

Eligibility

You can join if…

Open to people ages 12-65

for Part 1:

  1. Signs or symptoms consistent with an ALS disease process in the opinion of the Investigator
  2. 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 onset)

  1. 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
  2. Upright (sitting position) slow vital capacity (SVC) as adjusted for sex, age, and height ≥ 50 percentage (%) of predicted value
  3. 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
  4. 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.
  5. 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

Inclusion Criteria for Part 2:

  1. Completed, or rescued from, Part 1, or
  2. Enrolled and received at least 1 dose of ION363 in the Investigator-initiated EAP program
  3. Patient meeting Criteria #1-2 is otherwise suitable for study participation, in the opinion of the Investigator

You CAN'T join if...

for Part 1:

  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 for:
  4. Human immunodeficiency virus (HIV)
  5. Hepatitis C (HCV), unless previously treated and has been serum/plasma HCV RNA negative for at least 6 months after the end of treatment
  6. Hepatitis B (HBV) by HBV surface antigen test, unless currently on nucleotide/nucleoside analogue treatment
  7. 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
  8. Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm Hg])
  9. 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
  10. Obstructive hydrocephalus
  11. 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
  12. Concurrent participation in any other interventional clinical study
  13. . Previous treatment with an oligonucleotide (including small interfering RNA [siRNA]). This exclusion criterion does not apply to COVID-19 vaccinations, which are allowed
  14. . 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
  15. . History of gene therapy or cell transplantation or any other experimental brain surgery
  16. . 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

Locations

  • University of California San Diego accepting new patients
    La Jolla California 92037 United States
  • Stanford University Medical Center accepting new patients
    Palo Alto California 94304 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Ionis Pharmaceuticals, Inc.
ID
NCT04768972
Phase
Phase 3
Study Type
Interventional
Last Updated