A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD)

NCT04849741 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: ION373-CS12024-510603-11-00
• Study Type: interventional
• Target: 54
• Locations: 8 countries
• Sites: 13

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.

Conditions

Alexander Disease

Keywords

AxD

Outcome Measures

Primary Outcomes (1)

• Percent Change from Baseline in the 10-Meter Walk Test (10MWT)

  10-Meter Walk Test (10MWT) is an assessment of gait speed.

  Baseline and Week 61

Secondary Outcomes (15)

• Change From Baseline in Most Bothersome Symptom (MBS)

  Baseline and Week 61

• Change From Baseline in Patient Global Impression of Severity (PGIS) Score

  Baseline and Week 61

• Change From Baseline in Patient Global Impression of Change (PGIC) Score

  Baseline and Week 61

• Change From Baseline in Clinical Global Impression of Change (CGIC) Score

  Baseline and Week 61

• Change From Baseline in Gross Motor Function Measure-88, Dimensions C, D and E (GMFM-88, Dimensions C-E) Score

  Baseline and Week 61

Other Outcomes (1)

• Change From Baseline in Pediatrics Quality of Life Inventory (PedsQL) Generic Core Scales Score

  Baseline and Week 61

Study Arms (2)

zilganersen

EXPERIMENTAL

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.

Drug: zilganersen

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

zilganersen DRUG

zilganersen will be administered by ITB injection.

Also known as: ION373

zilganersen

Placebo DRUG

zilganersen-matching placebo will be administered by ITB injection.

Placebo

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Clinically significant abnormalities in medical history or physical examination
• 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)
• History of gene therapy or cell transplantation or any other experimental brain surgery \[ROW\]
• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (13)

Lucile Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

Location

Children's Hospital of Atlanta

Atlanta, Georgia, 30329, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

McGill University Health Centre

Montreal, Quebec, H3A 0G4, Canada

Location

Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Ospedale dei Bambini Vittore Buzzi

Milan, 20154, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, 165, Italy

Location

National Center of Neurology and Psychiatry

Tokyo, Kodaira-shi, 187-8551, Japan

Location

Amsterdam Universitair Medische Centra - Academisch Medisch Centrum

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

University College London Hospitals NHS Foundation Trust

London, WC1N 3BG, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Alexander Disease

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 19, 2021
• Study Start: June 1, 2021
• Primary Completion: August 22, 2025
• Study Completion (Estimated): September 1, 2029
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); GB (2); JP (1); IT (2); US (4); NL (1); IL (1); CA (1)