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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04849741




Registration number
NCT04849741
Ethics application status
Date submitted
16/04/2021
Date registered
19/04/2021

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD)
Scientific title
A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients With Alexander Disease
Secondary ID [1] 0 0
2024-510603-11-00
Secondary ID [2] 0 0
ION373-CS1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alexander Disease 0 0
Condition category
Condition code
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 - zilganersen
Treatment: Drugs - Placebo

Experimental: zilganersen - Zilganersen will be administered by intrathecal bolus (ITB) injection once every 12 weeks through Week 49. The 60-week double-blind treatment period will be followed by the open-label and long-term extension periods, where participants will receive zilganersen by ITB injection from Week 61 to Week 229.

Placebo comparator: Placebo - Matching placebo will be administered by ITB injection once every 12 weeks through Week 49. It will be followed by the open-label and long-term extension periods, where participants will receive zilganersen by ITB injection from Week 61 to Week 229.


Treatment: Drugs: zilganersen
zilganersen will be administered by ITB injection.

Treatment: Drugs: Placebo
zilganersen-matching placebo will be administered by ITB injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change from Baseline in the 10-Meter Walk Test (10MWT)
Timepoint [1] 0 0
Baseline and Week 61
Secondary outcome [1] 0 0
Change From Baseline in Most Bothersome Symptom (MBS)
Timepoint [1] 0 0
Baseline and Week 61
Secondary outcome [2] 0 0
Change From Baseline in Patient Global Impression of Severity (PGIS) Score
Timepoint [2] 0 0
Baseline and Week 61
Secondary outcome [3] 0 0
Change From Baseline in Patient Global Impression of Change (PGIC) Score
Timepoint [3] 0 0
Baseline and Week 61
Secondary outcome [4] 0 0
Change From Baseline in Clinical Global Impression of Change (CGIC) Score
Timepoint [4] 0 0
Baseline and Week 61
Secondary outcome [5] 0 0
Change From Baseline in Gross Motor Function Measure-88, Dimensions C, D and E (GMFM-88, Dimensions C-E) Score
Timepoint [5] 0 0
Baseline and Week 61
Secondary outcome [6] 0 0
Change From Baseline in 9-Hole Peg Test (9HPT) Score
Timepoint [6] 0 0
Baseline to Week 61
Secondary outcome [7] 0 0
Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Motor Skills Domain Score
Timepoint [7] 0 0
Baseline to Week 61
Secondary outcome [8] 0 0
Change From Baseline in Pediatrics Quality of Life Inventory Gastrointestinal Symptoms Scale (PedsQL GI) Score
Timepoint [8] 0 0
Baseline to Week 61
Secondary outcome [9] 0 0
Change From Baseline in Vineland Adaptive Behavior Composite, Third Edition (Vineland-3 ABC) Score
Timepoint [9] 0 0
Baseline to Week 61
Secondary outcome [10] 0 0
Change From Baseline in Composite Autonomic Symptom Score 31 (COMPASS-31) Score
Timepoint [10] 0 0
Baseline and Week 61
Secondary outcome [11] 0 0
Change From Baseline in Cerebrospinal Fluid (CSF) Glial Fibrillary Acid Protein (GFAP) Levels
Timepoint [11] 0 0
Baseline and Week 61
Secondary outcome [12] 0 0
Change From Baseline in Clinical Global Impression of Severity (CGIS) Score
Timepoint [12] 0 0
Baseline and Week 61
Secondary outcome [13] 0 0
Change From Baseline in Alexander Disease Patient Domain Impression of Severity (AxD-PDIS) Score
Timepoint [13] 0 0
Baseline and Week 61
Secondary outcome [14] 0 0
Change From Baseline in Alexander Disease Patient Domain Impression of Change (AxD-PDIC) Score
Timepoint [14] 0 0
Baseline and Week 61
Secondary outcome [15] 0 0
Change From Baseline in Body Weight Percentile (for participants < 18 years old at screening) or body weight (for participants = 18 years old at screening)
Timepoint [15] 0 0
Baseline and Week 61

Eligibility
Key inclusion criteria
Key

1. Clinical phenotype and brain imaging consistent with a diagnosis of Alexander disease
2. Documented genetic mutation in the GFAP gene
3. Aged = 2 to 65 years old at the time of informed consent
4. Able and willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits
5. Patients < 18 years old at Screening must have a trial partner (parent, caregiver or other)

Key
Minimum age
2 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically significant abnormalities in medical history or physical examination
2. Any clinically significant laboratory abnormalities that would render a patient unsuitable for inclusion
3. Any contraindication or unwillingness to undergo MRI
4. Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer; concurrent participation in any other clinical study (including observational and non-interventional studies)
5. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines (both messenger ribonucleic acid [mRNA] and viral vector vaccines).
6. History of gene therapy or cell transplantation or any other experimental brain surgery [ROW]
7. Obstructive hydrocephalus
8. Presence of a functional ventriculoperitoneal shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
9. Known brain or spinal disease that would interfere with the lumbar puncture (LP) process, CSF circulation or safety assessment.
10. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study
11. Have any other conditions, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient 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
1/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2029
Actual
Sample size
Target
73
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
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
Georgia
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
Pennsylvania
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Israel
State/province [6] 0 0
Tel Aviv
Country [7] 0 0
Italy
State/province [7] 0 0
Milan
Country [8] 0 0
Italy
State/province [8] 0 0
Roma
Country [9] 0 0
Japan
State/province [9] 0 0
Kodaira-shi
Country [10] 0 0
Netherlands
State/province [10] 0 0
Noord-Holland
Country [11] 0 0
United Kingdom
State/province [11] 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) 514-7157
Fax 0 0
Email 0 0
ionisNCT04849741study@clinicaltrialmedia.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/ionis/


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/study/NCT04849741