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

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of a new treatment called ION582 for individuals with Angelman syndrome, a genetic disorder affecting the nervous system and causing developmental issues. The treatment is administered through spinal injection over varying periods, depending on the study group. Individuals with a confirmed diagnosis of Angelman syndrome who have been on stable treatments for at least three months might be suitable candidates. The trial aims to determine if participants can safely use and tolerate this new treatment. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that ION582 is likely to be safe for humans?

Research has shown that ION582 is safe and well-tolerated in earlier studies. Participants tried different doses, and they generally handled the treatment well at all levels. No serious side effects emerged, suggesting that the treatment might be safe for people. This is encouraging news for those considering joining a clinical trial for Angelman syndrome. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Angelman Syndrome, which primarily focus on managing symptoms like seizures and behavioral issues, ION582 aims to address the condition at a genetic level. Researchers are excited about ION582 because it uses an intrathecal (IT) injection method to deliver the treatment directly to the central nervous system, potentially offering more direct and effective results. Additionally, ION582 targets the underlying genetic causes of Angelman Syndrome, offering hope for more substantial improvements in patient outcomes compared to current symptomatic treatments.

What evidence suggests that ION582 might be an effective treatment for Angelman syndrome?

Research indicates that ION582, the investigational treatment in this trial, may help treat Angelman syndrome. An earlier study showed that 97% of participants who received medium or high doses experienced symptom improvements after six months of treatment. The study also found ION582 to be safe and well tolerated. Overall, early results suggest that ION582 could enhance the quality of life for people with Angelman syndrome. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 F Experimental Treatment 1 Intervention

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 12 weeks between each dose administration.

Group VI: 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 VII: 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 VIII: 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 IX: 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 X: 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

Published Research Related to This Trial

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]

Citations

1. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-detailed-results-halos-study-ion582

Ionis announces positive detailed results from the HALOS ... Overall, 97% of people in the medium and high dose groups saw an improvement in overall AS symptoms as measured by the Symptoms of Angelman ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06914609

REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome The purpose of this study is to evaluate the efficacy and safety of ION582 in children and adults with Angelman syndrome caused by a deletion or mutation of the ...

3. neurologylive.com neurologylive.com/view/details-surrounding-phase-3-study-ion582-angelman-syndrome-announced

Details Surrounding Phase 3 Study of ION582 in Angelman ... After 6 months of treatment, 97% of the 51-patient cohort demonstrated clinically meaningful improvement on the Symptoms of Angelman Syndrome- ...

4. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-topline-results-phase-12a-trial-ion582

Ionis announces positive topline results from Phase 1/2a ... ION582 was safe and well tolerated in the study and showed encouraging and consistent benefits in individuals living with Angelman syndrome.

5. oligotherapeutics.org oligotherapeutics.org/angelman-syndrome-therapies-show-positive-results-in-early-phase-clinical-trials/

Angelman Syndrome Therapies Show Positive Results in ... Notably, after three doses and six months, 97% of people in the medium and high dose groups saw an improvement in overall AS symptoms as ...

6. ir.ionis.com ir.ionis.com/news-releases/news-release-details/first-patient-dosed-pivotal-phase-3-reveal-clinical-study-ion582

First patient dosed in pivotal Phase 3 REVEAL clinical ... The first participant has been dosed in the global Phase 3 REVEAL study, which is designed to evaluate the efficacy and safety of ION582, an investigational ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05127226

Study Details | NCT05127226 | HALOS: A Safety, ... The purpose of this study is to evaluate the safety and tolerability of ascending doses of ION582 administered intrathecally in participants with Angelman ...

8. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-ion582-for-patients-with-angelman-syndrome/

Study on the Safety and Effects of ION582 for Patients ... This study investigates the safety and effects of the antisense oligonucleotide ION582, administered intrathecally, for patients with the ...