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

JRCT ID: jRCT2031220465

Registered date:26/11/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Alexander disease
• Date of first enrollment: 14/12/2022
• Target sample size: 2
• Countries of recruitment: United States,Japan,Australia,Japan,Canada,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

- Experimental: ION373
ION373 will be administered by intrathecal bolus injection once every 12 weeks.

- Placebo Comparator: Placebo
ION373-matching placebo will be administered by intrathecal bolus injection once every 12 weeks through Week 60. Participants will then convert to ION373 administered by intrathecal bolus injection once every 12 weeks until end of the study.

Outcome(s)

• Primary Outcome: Percent change from Baseline in the 10-Meter Walk Test (10MWT) [ Time Frame: Baseline and Week 61 ]

Secondary Outcome

- Change From Baseline in Most Bothersome Symptom (MBS)
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Patient Global Impression of Severity (PGIS) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Patient Global Impression of Change (PGIC) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Clinical Global Impression of Change (CGIC) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Gross Motor Function Measure-88, Dimensions C, D and E (GMFM-88, Dimensions C-E) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in 9-Hole Peg Test (9HPT) Score
[ Time Frame: Baseline to Week 61 ]
- Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Motor Skills Domain Score
[ Time Frame: Baseline to Week 61 ]
- Change From Baseline in Pediatrics Quality of Life Inventory Gastrointestinal Symptoms Scale (PedsQL GI) Score
[ Time Frame: Baseline to Week 61 ]
- Change From Baseline in Vineland Adaptive Behavior Composite, Third Edition (Vineland-3 ABC) Score
[ Time Frame: Baseline to Week 61 ]
- Change From Baseline in Composite Autonomic Symptom Score 31 (COMPASS-31) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Cerebrospinal Fluid (CSF) Glial Fibrillary Acid Protein (GFAP) Levels
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Clinical Global Impression of Severity (CGIS) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Alexander Disease Patient Domain Impression of Severity (AxD-PDIS) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Alexander Disease Patient Domain Impression of Change (AxD-PDIC) Score
[ Time Frame: Baseline and Week 61 ]
- Change From Baseline in Body Weight Percentile (for participants < 18 years old at screening) or body weight (for participants >= 18 years old at screening)
[ Time Frame: Baseline and Week 61 ]

Key inclusion & exclusion criteria

• Age minimum: >= 2age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

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

Exclude criteria

- Clinically significant abnormalities in medical history or physical examination
- Any clinically significant laboratory abnormalities that would render a patient unsuitable for inclusion
- Any contraindication or unwillingness to undergo MRI
- 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)
- 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).
- History of gene therapy or cell transplantation or any other experimental brain surgery
- Obstructive hydrocephalus
- Presence of a functional ventriculoperitoneal shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
- Known brain or spinal disease that would interfere with the lumbar puncture (LP) process, CSF circulation or safety assessment.
- Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study
- 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

Related Information

• Primary Sponsor: Deurell Erik
• Secondary ID(s): NCT04849741