What side effects are associated with this type of intervention?

Intrathecal administration of treatments for Angelman Syndrome, such as the investigational drug ION582, primarily aims to evaluate safety and tolerability. Common side effects associated with intrathecal treatments can include headache, back pain, nausea, and potential infection at the injection site. More broadly, treatments for Angelman Syndrome may also involve antiepileptic drugs, which can cause drowsiness, dizziness, and gastrointestinal issues. It is essential to monitor for these side effects and discuss them with a healthcare provider.

What prior FDA approvals exist?

Currently, there is limited information on FDA-approved treatments specifically for Angelman Syndrome, particularly those involving intrathecal administration like ION582. The trial mentioned is focused on evaluating the safety and tolerability of ION582 administered intrathecally in participants with Angelman Syndrome. This suggests that research is ongoing to find effective treatments for this condition, but specific FDA-approved drugs or similar treatments are not detailed in the provided context.

What other types of research exist?

Promising novel alternatives to ION582 for Angelman Syndrome patients include gene therapies such as GTX-102, which targets the UBE3A gene, and pharmacological treatments like OV101 (gaboxadol), which modulates the GABAergic system. Both have shown potential in clinical trials for improving symptoms associated with Angelman Syndrome.

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Antisense Oligonucleotide

ION582 for Angelman Syndrome

Phase 1 & 2

Waitlist Available

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Male or female between the ages of 2-50 years of age, with signed informed consent from parent(s) or legal guardian(s)

Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation)

Must not have

Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID)

Any prior use of gene therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up part 1: up to week 45; part 2: up to week 81

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a drug called ION582, given directly into the spinal fluid, to see if it is safe for people with Angelman syndrome. The study will check how well patients tolerate different doses of the drug.

Who is the study for?

This trial is for individuals aged 2-50 with a certified diagnosis of Angelman syndrome, who have been on stable standard care treatments and medications for at least 3 months. They must not share study info on social media until the study ends. Excluded are those with certain genetic profiles, risks from lumbar puncture, previous oligonucleotide treatment or gene therapy, uncontrolled seizures, or other significant health issues.

What is being tested?

The HALOS trial is testing ION582 given intrathecally (directly into the spinal canal) to see how safe it is and how well tolerated in different doses among participants with Angelman syndrome. The focus is on understanding the drug's effects and how it moves through and out of the body.

What are the potential side effects?

While specific side effects aren't listed here, common ones related to intrathecal administration may include headache, back pain, nausea or vomiting. There could also be potential reactions at the injection site or systemic effects depending on how ION582 works in the body.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 2 and 50 years old and have consent from my parent or guardian.

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I have been diagnosed with Angelman syndrome.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My condition is confirmed to be due to specific genetic changes.

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I have previously undergone gene therapy.

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I have a condition that could make a spinal tap risky or difficult.

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I have had severe seizures or a dangerous seizure condition in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ part 1: up to week 45; part 2: up to week 81

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~part 1: up to week 45; part 2: up to week 81

This trial's timeline: 3 weeks for screening, Varies for treatment, and part 1: up to week 45; part 2: up to week 81 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To evaluate the safety and tolerability of single and multiple doses of ION582 (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters).

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Part 3 Group 2Experimental Treatment1 Intervention

ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.

Group II: Part 3 Group 1Experimental Treatment1 Intervention

ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.

Group III: Part 2 Group 2Experimental Treatment1 Intervention

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Group IV: Part 2 Group 1Experimental Treatment1 Intervention

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Group V: Part 1 MAD: Cohort EExperimental Treatment1 Intervention

ION582 will be administered as IT injection of over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Group VI: Part 1 MAD: Cohort DExperimental Treatment1 Intervention

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Group VII: Part 1 MAD: Cohort CExperimental Treatment1 Intervention

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Group VIII: Part 1 MAD: Cohort BExperimental Treatment1 Intervention

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Group IX: Part 1 MAD: Cohort AExperimental Treatment1 Intervention

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Angelman Syndrome often target the neurological symptoms, such as seizures and motor dysfunction. One such treatment is the intrathecal administration of medications, which involves delivering drugs directly into the cerebrospinal fluid to bypass the blood-brain barrier, ensuring higher concentrations in the central nervous system. This method is being studied in the trial ION582. The primary mechanism of action for these treatments is to modulate neurotransmitter activity and improve synaptic function, which can help alleviate symptoms like seizures, improve motor skills, and enhance cognitive functions. This is crucial for Angelman Syndrome patients as it directly addresses the neurological deficits that significantly impact their quality of life.

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