HALOS: increasing spinal doses of ION582 for people with Angelman syndrome

HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome

This trial will try repeated spinal (intrathecal) injections of ION582 in people with Angelman syndrome to check safety, how the drug acts in the body, and early effects.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 0 Years to 50 Years
• Sex: All
• Sponsor: Ionis Pharmaceuticals, Inc. (Industry-sponsored)
• Locations: 11 sites (San Diego, California and 10 other locations)
• Trial ID: NCT05127226 on ClinicalTrials.gov

What this trial studies

HALOS is an open-label Phase 1–2a trial testing multiple ascending intrathecal doses of ION582 in roughly 70 participants with genetically confirmed Angelman syndrome. The program has three parts: Part 1 is a 13-week multiple ascending dose period plus at least 12 weeks of follow-up, Part 2 is a 49-week multi-center dosing period with a minimum 12-week follow-up for those who complete Part 1, and Part 3 is an extension of up to an additional 3 years followed by a 32-week post-extension follow-up. The primary focus is safety, tolerability, pharmacokinetics, and pharmacodynamics, and the study is open-label without placebo. The protocol enrolls participants aged 0–50 with UBE3A deletion or mutation (an amendment added a cohort under age 2) and excludes individuals with UPD or imprinting defects.

Who should consider this trial

Good fit: Ideal candidates are people aged 0–50 with a confirmed UBE3A deletion or mutation who are medically stable on current treatments and can undergo intrathecal dosing with parental or guardian consent as needed.

Not a fit: People with Angelman syndrome caused by paternal uniparental disomy or imprinting defects, those who cannot tolerate spinal injections, or those with unstable medical conditions are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could demonstrate a tolerable way to deliver ION582 into the spinal fluid and show biological or clinical signs of benefit for people with Angelman syndrome.

How similar studies have performed: Antisense and intrathecal strategies for Angelman syndrome are relatively new and have limited clinical data so far, with safety signals reported but no definitive, widely replicated clinical benefit.

Eligibility criteria

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.

Where this trial is running

San Diego, California and 10 other locations

• Rady Children's Hospital — San Diego, California, United States (Recruiting)
• Colorado Children's Hospital Research Institute — Aurora, Colorado, United States (Recruiting)
• Rush University Medical Center — Chicago, Illinois, United States (Recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• University of North Carolina at Chapel Hill School of Medicine — Carrboro, North Carolina, United States (Recruiting)
• Texas Children's Hospital — Houston, Texas, United States (Active_not_recruiting)
• Sydney Children's Hospital, Kids Cancer Centre — Randwick, Australia (Active_not_recruiting)
• Necker-Enfants Malades Hospital — Paris, France (Recruiting)
• Sheba Medical Center — Ramat Gan, Israel (Recruiting)
• Azienda Ospedaliera Universitaria Pisana — Pisa, Italy (Recruiting)
• STRONG Group University of Oxford — Oxford, Oxfordshire, United Kingdom (Active_not_recruiting)

Study contacts

• Study coordinator: Ionis Pharmaceuticals

Conditions Angelman Syndrome