ION582 for Angelman Syndrome

Recruiting at 10 trial locations

Overseen By Ionis Pharmaceuticals

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ionis Pharmaceuticals, Inc.

Must be taking: Anti-epileptic, Behavioral, Sleep, Gabapentin

Must not be taking: Oligonucleotides, Gene therapy

Disqualifiers: Uniparental disomy, Poorly controlled seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

51 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. In fact, you need to be on stable doses of your standard treatments, like anti-epileptic or sleep medications, for at least 3 months before starting the trial.

How does the drug ION582 differ from other treatments for Angelman Syndrome?

ION582 is unique because it targets the underlying genetic cause of Angelman Syndrome by addressing the deficiency of the UBE3A gene, which is not the focus of most existing treatments that primarily manage symptoms like seizures. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

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.

Inclusion Criteria

I have been on a stable treatment plan for my condition, including medications and diets, for at least 3 months.

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

I have been diagnosed with Angelman syndrome.

Exclusion Criteria

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

Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion or could interfere with the participant taking part in or completing the study

I have previously undergone gene therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Multiple Ascending Dose (MAD) Treatment

Participants receive multiple ascending doses of ION582 administered intrathecally over a 13-week period

13 weeks

Approximately 4 weeks between each dose administration

Part 1: Post-MAD Follow-Up

Participants are monitored for safety and effectiveness after the MAD treatment

12-32 weeks

Part 2: Treatment

Participants receive IT bolus doses of ION582 over a 49-week period

49 weeks

Part 2: Follow-Up

Participants are monitored for safety and effectiveness after Part 2 treatment

12 weeks

Part 3: Long-Term Extension (LTE) Treatment

Participants receive extended treatment with ION582 for up to an additional 3 years

145 weeks

Part 3: Post-LTE Follow-Up

Participants are monitored for safety and effectiveness after the LTE treatment

32 weeks

Treatment Details

Interventions

• ION582

Trial Overview 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.

Participant Groups

Group I: Part 3 Group 2 Experimental Treatment 1 Intervention

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

Group II: Part 3 Group 1 Experimental Treatment 1 Intervention

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

Group III: Part 2 Group 2 Experimental Treatment 1 Intervention

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

Group IV: Part 2 Group 1 Experimental Treatment 1 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 E Experimental Treatment 1 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 D Experimental Treatment 1 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 C Experimental Treatment 1 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 B Experimental Treatment 1 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 A Experimental Treatment 1 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.

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

Biogen

Industry Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Findings from Research

In a study involving 7 patients with Angelman syndrome (AS) and 4 healthy controls, GABA(A) receptor expression was found to be significantly higher in the cerebral cortex and cerebellum of patients with certain genotypes, indicating a potential alteration in receptor function.

The findings suggest that there is a developmental dysregulation of GABA(A) receptor subunits in AS, which could have implications for understanding the neurological aspects of the syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(11)C]flumazenil positron emission tomography analyses of brain gamma-aminobutyric acid type A receptors in Angelman syndrome. Asahina, N., Shiga, T., Egawa, K., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations. [2022]

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

[(11)C]flumazenil positron emission tomography analyses of brain gamma-aminobutyric acid type A receptors in Angelman syndrome. [2016]

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

Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome. [2016]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Epilepsy in Korean patients with Angelman syndrome. [2021]

5. Iran pubmed.ncbi.nlm.nih.gov

Angelman Syndrome: A Case Report. [2023]