Zilganersen for Alexander Disease

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

73 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called zilganersen to see if it can help people with Alexander Disease improve or keep their ability to move. The study involves giving the drug in different doses to find out its effects on movement abilities.

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 Zilganersen (ION373) safe for humans?

The safety of nusinersen, a similar treatment, has been studied in patients with spinal muscular atrophy (SMA), showing it to be generally safe with no new safety concerns in multiple studies involving both children and adults. ^{1 2 3 4 5}

How is the drug Zilganersen (ION373) for Alexander Disease different from other treatments?

Zilganersen (ION373) is unique because it is an antisense oligonucleotide (a type of genetic therapy) similar to nusinersen, which is used for spinal muscular atrophy. This approach targets the genetic cause of the disease, offering a novel mechanism of action compared to traditional treatments, and is administered intrathecally (directly into the spinal fluid). ^{1 3 5 6 7}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. [2018]

3. England 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The Antisense Oligonucleotide Nusinersen for Treatment of Spinal Muscular Atrophy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Implementing a Global Expanded Access Program (EAP) for Infantile-Onset Spinal Muscular Atrophy (Type I): Understanding the Imperative, Impact and Challenges. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters. [2022]