Back to Trials
NCT05127226PHASE1, PHASE2Recruiting

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome

Ionis Pharmaceuticals, Inc.

Start Date

12/22/2021

Completion Date

3/1/2029

Summary

The purpose of this study is to evaluate the safety and tolerability of ascending doses of ION582 administered intrathecally in participants with Angelman syndrome.

Detailed Description

This is a Phase 1-2a, open-label study consisting of 3 parts in approximately 70 participants. Part 1 is a multiple ascending dose (MAD) study, consisting of a 13-week MAD Treatment Period and a minimum 12-week Post-MAD Follow-Up Period. Part 2 is a multi-center 49-week study where participants who completed Part 1 will receive IT bolus doses of ION582 followed by a minimum 12-week Part 2 follow up period. Part 3 extends the treatment period for participants who completed Part 2 for up to an additional 3 years followed by a 32-week post-LTE follow up period. The study was amended in late 2025 to include a cohort of people with Angelman Syndrome under the age of 2 years old. Recruitment sites listed as "Recruiting" below are eligible to recruit individuals into this new cohort only. This page will continue to be updated to reflect the recruitment status of sites and the study. For more information, speak with your doctor or see the Study Contact information below.

Eligibility Criteria

Age Range: No minimum to 50 years

Key Inclusion Criteria: 1. Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A \[UBE3A\] deletion or UBE3A mutation) 2. Male or female between the ages of 0-50 years of age, with signed informed consent from parent(s) or legal guardian(s) 3. Currently receiving stable standard of care treatments such as, stable doses of anti-epileptic medication, behavioral management medications, sleep medications, gabapentin, cannabidiol, and including special diets, supplements or nutritional support for at least 3 months prior to first dose. 4. Follow good study practice and not participate in the sharing of personal or study information on social media platforms, such as any website or social media site (e.g., Facebook, Instagram, Twitter, YouTube, etc.) until notified that the study is completed. Key Exclusion Criteria: 1. Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID). 2. Any clinically significant (CS) cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, will make the patient unsuitable for participation in, and/or unable to complete the study procedures. Has poorly controlled seizures as determined by the Investigator or has documented Status Epilepticus in the past 6 months that could pose a safety risk while on study. 3. Known bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid, antisense oligonucleotide \[ASOs\]). COVID-19 vaccinations are allowed. 4. Any prior use of gene therapy. 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.

Interventions

DRUG

ION582

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Angelman Syndrome

Locations

Rady Children's Hospital

San Diego, California 92123

United States

Colorado Children's Hospital Research Institute

Aurora, Colorado 80045

United States

Rush University Medical Center

Chicago, Illinois 60612

United States

Boston Children's Hospital

Boston, Massachusetts 02215

United States

University of North Carolina at Chapel Hill School of Medicine

Carrboro, North Carolina 27510

United States

Texas Children's Hospital

Houston, Texas 77030

United States

Sydney Children's Hospital, Kids Cancer Centre

Randwick, NSW 2031

Australia

Necker-Enfants Malades Hospital

Paris, 75015

France

Sheba Medical Center

Ramat Gan, 5262100

Israel

Azienda Ospedaliera Universitaria Pisana

Pisa, 56126

Italy

STRONG Group University of Oxford

Oxford, Oxfordshire OX3 9DU

United Kingdom