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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04849741
Registration number
NCT04849741
Ethics application status
Date submitted
16/04/2021
Date registered
19/04/2021
Date last updated
30/01/2024
Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of ION373 in Patients With Alexander Disease (AxD)
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Scientific title
A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered Zilganersen (ION373) in Patients With Alexander Disease
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Secondary ID [1]
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2020-000976-40
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Secondary ID [2]
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ION373-CS1
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alexander Disease
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Condition category
Condition code
Neurological
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Neurodegenerative diseases
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percent Change from Baseline in the 10-Meter Walk Test (10MWT)
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Assessment method [1]
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Timepoint [1]
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Baseline and Week 61
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Secondary outcome [1]
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Change From Baseline in Most Bothersome Symptom (MBS)
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Assessment method [1]
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Timepoint [1]
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Baseline and Week 61
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Secondary outcome [2]
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Change From Baseline in Patient Global Impression of Severity (PGIS) Score
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Assessment method [2]
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The PGIS questionnaire captures the participant's rating of the severity of his/her global health status associated with AxD on a 5-point ordinal scale.
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Timepoint [2]
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Baseline and Week 61
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Secondary outcome [3]
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Change From Baseline in Patient Global Impression of Change (PGIC) Score
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Assessment method [3]
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The PGIC questionnaire captures the participant's rating of improvement or decline in his/her global health status on a 5-point ordinal scale.
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Timepoint [3]
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Baseline and Week 61
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Secondary outcome [4]
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Change From Baseline in Clinical Global Impression of Change (CGIC) Score
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Assessment method [4]
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The CGIC questionnaire captures the participant's rating of improvement or decline in his/her global health status on a 5-point ordinal scale.
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Timepoint [4]
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Baseline and Week 61
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Secondary outcome [5]
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Change From Baseline in Gross Motor Function Measure-88, Dimensions C, D and E (GMFM-88, Dimensions C-E) Score
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Assessment method [5]
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The GMFM-88 is a standardized observational instrument to measure change in gross motor function over time in children with developmental disabilities consisting of 88 items scored on a 4-point ordinal scale grouped in 5 dimensions. Dimensions C (crawling and kneeling), D (standing) and E (walking, running & jumping) will be assessed. The goal total score is the average of the dimension scores expressed as a percentage of the maximum score for that dimension.
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Timepoint [5]
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Baseline and Week 61
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Secondary outcome [6]
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Change From Baseline in 9-Hole Peg Test (9HPT) Score
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Assessment method [6]
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The 9HPT is a simple test of manual dexterity that records the time required for the participant to accurately place and remove nine pegs into a pegboard.
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Timepoint [6]
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Baseline to Week 61
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Secondary outcome [7]
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Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Motor Skills Domain Score
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Assessment method [7]
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The Vineland-3 is a standardized measure used to quantify adaptive behaviors necessary for socialization, communication and daily functioning. Items are scored on a 0-2 scale rating the consistency of independent completion of the assessed skill.
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Timepoint [7]
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Baseline to Week 61
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Secondary outcome [8]
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Change From Baseline in Pediatrics Quality of Life Inventory Gastrointestinal Symptoms Scale (PedsQL GI) Score
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Assessment method [8]
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The PedsQL GI Symptoms Scales captures gastrointestinal symptoms on 10 scales and 58 items: Stomach Pain and Hurt Scale (6 items), Stomach Discomfort When Eating Scale (5 items), Food and Drink Limits Scale (6 items), Trouble Swallowing Scale (3 items), Heartburn and Reflux Scale (4 items), Nausea and Vomiting Scale (4 items), Gas and Bloating Scale (7 items), Constipation Scale (14 items), Blood in Poop Scale (2 items) and Diarrhea Scale (7 items). Higher scores indicate few symptoms and better GI-specific health-related quality of life.
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Timepoint [8]
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Baseline to Week 61
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Secondary outcome [9]
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Change From Baseline in Vineland Adaptive Behavior Composite, Third Edition (Vineland-3 ABC) Score
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Assessment method [9]
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The Vineland-3 is a standardized measure used to quantify adaptive behaviors necessary for socialization, communication and daily functioning. The Core Adaptive Behavior Scores encompass 3 domains of behavior: communication, daily living and socialization. Items are scored on a 0-2 scale rating the consistency of independent completion of the assessed skill.
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Timepoint [9]
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Baseline to Week 61
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Secondary outcome [10]
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Change From Baseline in Composite Autonomic Symptom Score 31 (COMPASS-31) Score
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Assessment method [10]
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COMPASS-31 is a 31-question participant-reported assessment that measures autonomic symptoms across 6 weighted domains on a 100-point scale: orthostatic intolerance (40 points), vasomotor (5 points), secretomotor (15 points), gastrointestinal (25 points), bladder (10 points), and pupillomotor (15 points). A higher score indicates worse autonomic dysfunction.
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Timepoint [10]
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Baseline and Week 61
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Secondary outcome [11]
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Change From Baseline in Cerebrospinal Fluid (CSF) Glial Fibrillary Acid Protein (GFAP) Levels
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Assessment method [11]
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Timepoint [11]
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Baseline and Week 61
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Secondary outcome [12]
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Change From Baseline in Clinical Global Impression of Severity (CGIS) Score
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Assessment method [12]
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The CGIS questionnaire captures the clinician's rating of the severity of the participant's global health status associated with AxD on a 5-point ordinal scale.
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Timepoint [12]
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Baseline and Week 61
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Secondary outcome [13]
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Change From Baseline in Alexander Disease Patient Domain Impression of Severity (AxD-PDIS) Score
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Assessment method [13]
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The AxD-PDIS questionnaire captures the participant's rating of the severity of specific disease symptoms including gross and fine motor problems, GI problems, language or speech problems and other cognitive problems.
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Timepoint [13]
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Baseline and Week 61
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Secondary outcome [14]
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Change From Baseline in Alexander Disease Patient Domain Impression of Change (AxD-PDIC) Score
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Assessment method [14]
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The AxD-PDIC questionnaire captures the participant's rating of improvement or decline in specific disease symptoms including gross and fine motor problems, GI problems, language or speech problems and other cognitive problems.
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Timepoint [14]
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Baseline and Week 61
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Secondary outcome [15]
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Change From Baseline in Body Weight Percentile (for participants < 18 years old at screening) or body weight (for participants = 18 years old at screening)
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Assessment method [15]
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Timepoint [15]
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Baseline and Week 61
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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)
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Minimum age
2
Years
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Maximum age
65
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/06/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/03/2029
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Actual
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Sample size
Target
73
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Murdoch Children's Research Institute - Parkville
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Recruitment postcode(s) [1]
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3052 - Parkville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Georgia
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Country [3]
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United States of America
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State/province [3]
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Massachusetts
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Country [4]
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United States of America
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State/province [4]
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Pennsylvania
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Country [5]
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Canada
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State/province [5]
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Quebec
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Country [6]
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Israel
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State/province [6]
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Tel Aviv
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Country [7]
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Italy
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State/province [7]
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Milan
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Country [8]
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Italy
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State/province [8]
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Roma
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Country [9]
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Japan
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State/province [9]
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Kodaira-shi
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Country [10]
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Netherlands
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State/province [10]
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Noord-Holland
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Country [11]
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United Kingdom
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State/province [11]
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Ionis Pharmaceuticals, Inc.
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to evaluate the safety and efficacy of zilganersen (ION373) in
improving or stabilizing gross motor function across the full range of affected domains in
patients with AxD.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04849741
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Ionis Pharmaceuticals
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Address
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Country
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Phone
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(844) 514-7157
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04849741
Download to PDF