Zilganersen for Alexander Disease

No longer recruiting at 14 trial locations

Overseen By Ionis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Ionis Pharmaceuticals, Inc.

Must not be taking: Investigational drugs, Oligonucleotides

Disqualifiers: Obstructive hydrocephalus, Brain disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests zilganersen, a new treatment for Alexander disease, a rare disorder affecting the brain and spinal cord. The study aims to determine if zilganersen can improve or stabilize patients' mobility. Participants will receive either the treatment or a placebo (a harmless, inactive substance) through regular injections. This trial may suit individuals diagnosed with Alexander disease, confirmed by specific genetic testing. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken another investigational drug recently or have a history of certain treatments like gene therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zilganersen, the treatment under study for Alexander Disease, was safe in earlier studies. In those studies, zilganersen helped stabilize patients' movement abilities, indicating its safety. While specific side effects were not detailed, the treatment's progression to this advanced stage suggests it is safe enough for further testing. Additionally, since zilganersen aims to improve movement, it appears to be generally well-tolerated by participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alexander Disease?

Unlike the standard of care for Alexander Disease, which primarily focuses on managing symptoms, Zilganersen offers a novel approach. It is administered directly into the spinal fluid via an intrathecal bolus injection, allowing for targeted delivery. This treatment works by addressing the underlying genetic cause of the disease, aiming to modify its progression rather than just alleviating symptoms. Researchers are particularly excited about Zilganersen because it could represent a breakthrough in slowing or even halting the neurological decline associated with Alexander Disease.

What evidence suggests that zilganersen might be an effective treatment for Alexander Disease?

Research has shown that zilganersen, which participants in this trial may receive, may help treat Alexander Disease (AxD). In one study, patients who took zilganersen walked faster over a short distance. Those who received a higher dose improved their ability to walk 10 meters by 33.3%. Zilganersen also aided with other movement-related issues. These findings suggest that the treatment might help maintain or improve movement abilities in people with AxD. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for people aged 2 to 65 with Alexander Disease (AxD), confirmed by specific brain imaging and a genetic mutation in the GFAP gene. Children under 18 need a caregiver to participate. Participants must be able to travel for study requirements but can't join if they've had recent major surgery, other experimental brain treatments, or are on another clinical trial.

Inclusion Criteria

Able and willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits

Your symptoms and brain scan show signs of having Alexander disease.

You have a confirmed genetic mutation in the GFAP gene.

Exclusion Criteria

Any contraindication or unwillingness to undergo MRI

History of gene therapy or cell transplantation or any other experimental brain surgery [ROW]

You have a brain or spinal condition that could make it unsafe for you to have a lumbar puncture.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive zilganersen or placebo by intrathecal bolus injection every 12 weeks for 60 weeks

60 weeks

5 visits (in-person)

Open-label Treatment

All participants receive zilganersen by intrathecal bolus injection every 12 weeks for 60 weeks

60 weeks

5 visits (in-person)

Long-term Extension

Participants continue to receive zilganersen by intrathecal bolus injection every 12 weeks for 120 weeks

120 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ION373
• Placebo

Trial Overview

The study tests zilganersen (ION373) against a placebo to see if it improves or stabilizes gross motor function in AxD patients. It's designed to compare the effects of this potential new treatment with no active treatment over time.

How Is the Trial Designed?

Group I: zilganersen Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Published Research Related to This Trial

In a study of 52 spinal muscular atrophy (SMA) patients treated with nusinersen, significant improvements in motor function were observed in pediatric patients with SMA types 1 and 2 after receiving the drug, particularly after four doses.

Nusinersen was found to be safe, with no new safety concerns reported during the administration of 437 doses; however, adult patients with SMA type 3 who started treatment after age 18 did not show significant improvements in motor performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data. Belančić, A., Strbad, T., Kučan Štiglić, M., et al.[2023]

In a post-marketing surveillance study of 524 patients treated with nusinersen for spinal muscular atrophy (SMA), the treatment showed significant safety and effectiveness, with 35.9% of patients experiencing adverse events, mostly mild to moderate.

Nusinersen significantly improved motor function in patients with both infantile-onset and later-onset SMA, with 98.5-100% of patients reporting improvement or no change in their condition after nearly 3 years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 524 patients: results from an interim analysis of post-marketing surveillance in Japan. Tachibana, Y., Sato, R., Makioka, H., et al.[2023]

Citations

1.

ir.ionis.com

ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-topline-results-pivotal-study

Ionis announces positive topline results from pivotal study ...

Zilganersen 50 mg demonstrated statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed as ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04849741

A Study to Evaluate the Safety and Efficacy of Zilganersen ...

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 ...

3.

ulf.org

ulf.org/2025/09/positive-results-announced-for-alexander-disease-clinical-trial/

Positive Results Announced for Alexander Disease Clinical ...

Zilganersen also demonstrated consistent benefit in key secondary endpoints. These data mark the first time an investigational medicine has ...

4.

neurologylive.com

neurologylive.com/view/ionis-plans-application-submission-zilganersen-potential-first-treatment-alexander-disease-following-positive-data

Ionis Plans Application Submission for Zilganersen as ...

Zilganersen showed significant disease-modifying effects in AxD, with a 33.3% improvement in the 10-Meter Walk Test for the higher dose group.

5.

empr.com

empr.com/news/zilganersen-improves-functional-mobility-in-patients-with-alexander-disease/

Zilganersen Improves Functional Mobility in Patients With ...

Findings showed patients treated with zilganersen 50mg demonstrated statistically significant and clinically meaningful improvement from ...

6.

neurologyadvisor.com

neurologyadvisor.com/news/zilganersen-improves-functional-mobility-in-patients-with-alexander-disease/

Zilganersen Improves Functional Mobility in Patients With ...

Topline data were announced from a pivotal study evaluating zilganersen in children and adults living with Alexander disease.