Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04768972




Registration number
NCT04768972
Ethics application status
Date submitted
22/02/2021
Date registered
24/02/2021
Date last updated
15/09/2023

Titles & IDs
Public title
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
Scientific 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)
Secondary ID [1] 0 0
2020-005522-28
Secondary ID [2] 0 0
ION363-CS1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ION363
Treatment: Drugs - Placebo

Experimental: ION363 - ION363 will be administered by lumbar intrathecal (IT) bolus injection with 1 dose every 4-12 weeks, after a loading dose at 4 weeks, over a 61-week double-blind treatment period in Part 1 and every 12 weeks for 85 weeks in the open-label extension treatment period, aside from a loading dose administered 4 weeks after the first dose in Part 2.

Placebo Comparator: Placebo - Placebo will be administered by lumbar IT bolus injection with 1 dose every 4-12 weeks over a 61-week double-blind treatment period.


Treatment: Drugs: ION363
ION363 will be administered by IT bolus injection.

Treatment: Drugs: Placebo
Placebo will be administered by IT bolus injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline (Day 1) through Study Day 505 in Part 1 in functional impairment
Timepoint [1] 0 0
Baseline, Day 505 in Part 1
Secondary outcome [1] 0 0
Change From Baseline in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) Score to Day 505 in Part 1
Timepoint [1] 0 0
Baseline, Day 505 in Part 1
Secondary outcome [2] 0 0
Change from Baseline in in-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Timepoint [2] 0 0
Baseline, Day 505 in Part 1
Secondary outcome [3] 0 0
Survival
Timepoint [3] 0 0
Up to Day 505 in Part 1
Secondary outcome [4] 0 0
Change From Baseline in In-clinic Slow Vital Capacity (SVC) to Day 505 in Part 1
Timepoint [4] 0 0
Baseline, Day 505 in Part 1
Secondary outcome [5] 0 0
Change From Baseline in Handheld Dynamometry (HHD) to Day 505 in Part 1
Timepoint [5] 0 0
Baseline, Day 505 in Part 1
Secondary outcome [6] 0 0
Change From Baseline in Neurofilament Light (NfL) Concentration in Cerebrospinal Fluid (CSF) to Day 505
Timepoint [6] 0 0
Baseline, Day 505 in Part 1

Eligibility
Key inclusion criteria
Inclusion Criteria for Part 1:

1. Participants in:

Cohort A must be 12 - 65 years of age with signs or symptoms consistent with an ALS
disease. If 30 to 65 years of age, 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> 30 years of age, with signs or symptoms consistent with an ALS
disease process 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). If
between the ages of 30 - 65 years, inclusive, or > 65 years of age with no ALSFRS-R
pre-study slope criterion

2. Confirmed genetic mutation in FUS in a clinical laboratory improvement amendments
(CLIA) certified, CE-marked, or equivalent testing laboratory. Mutations must be
reviewed and approved by a variant classification committee.

3. Upright (sitting position) slow vital capacity (SVC) as adjusted for sex, age, and
height = 50 percent (%) of predicted value

4. 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

5. Stable accompanied medications and nutritional support for at least 1 month prior to
Study Day 1. Accompanied 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.

6. 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria 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:

1. Human immunodeficiency virus (HIV)

2. Hepatitis C (HCV), unless previously treated and has been serum/plasma HCV RNA
negative for at least 6 months after the end of treatment

3. Hepatitis B (HBV) by HBV surface antigen test, unless currently on
nucleotide/nucleoside analogue treatment

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

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 per
Investigator judgement.

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]).
This exclusion criterion does not apply to COVID-19 vaccinations, which are allowed

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2028
Actual
Sample size
Target
77
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Belgium
State/province [8] 0 0
VL-Brabant
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Italy
State/province [10] 0 0
Torino
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Netherlands
State/province [12] 0 0
Utrecht
Country [13] 0 0
United Kingdom
State/province [13] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ionis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ionis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
(844) 421-0104
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/ct2/show/NCT04768972