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

Brief Title

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

Official Title

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

Brief 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 dose-escalation study of ION582 enrolling up to
      approximately 44 participants. Following a screening period of up to 4 weeks, eligible
      participants will receive intrathecal (IT) injections of ION582. Participants will be
      followed for up to 32 weeks after dosing.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

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).

Secondary Outcome

 Maximum Observed Plasma Concentration (Cmax) of ION582


Angelman Syndrome



Study Arms / Comparison Groups

 Cohort A: Dose 1
Description:  ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

November 2021

Completion Date

December 2023

Primary Completion Date

July 2023

Eligibility Criteria

        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 2-50 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

        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.




2 Years - 50 Years

Accepts Healthy Volunteers



, 800-679-4747, [email protected]

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Ionis Pharmaceuticals, Inc.

Study Sponsor

, , 

Verification Date

November 2021