Angelman SyndromePhase 1/2NCT05127226
HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
A Phase 1/2 study testing ION582 in people with Angelman Syndrome, run by Ionis Pharmaceuticals, Inc. at 11 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 50 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- ION582
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 22 Dec 2021to Mar 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation)
- Male or female between the ages of 0-50 years of age, with signed informed consent from parent(s) or legal guardian(s)
- 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.
- 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.
Who cannot join
- Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID).
- 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.
- 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.
- 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.
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
United States6 sites
Colorado Children's Hospital Research Institute
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02215
University of North Carolina at Chapel Hill School of Medicine
Carrboro, North Carolina, 27510
Rush University Medical Center
Chicago, Illinois, 60612
Texas Children's Hospital
Houston, Texas, 77030
Rady Children's Hospital
San Diego, California, 92123
Australia1 site
Sydney Children's Hospital, Kids Cancer Centre
Randwick, NSW 2031
United Kingdom1 site
STRONG Group University of Oxford
Oxford, Oxfordshire, OX3 9DU
About this study
Official title: HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome
The purpose of this study is to evaluate the safety and tolerability of ascending doses of ION582 administered intrathecally in participants with Angelman syndrome.
Read the 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.
- Conditions
- Angelman Syndrome
- Being tested
- ION582
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION582Drug
ION582 will be administered by IT injection.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 MAD: Cohort A | Experimental | ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. Receives: Drug: ION582 |
| Part 1 MAD: Cohort B | Experimental | ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. Receives: Drug: ION582 |
| Part 1 MAD: Cohort C | Experimental | ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. Receives: Drug: ION582 |
| Part 1 MAD: Cohort D | Experimental | ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. Receives: Drug: ION582 |
| Part 1 MAD: Cohort E | Experimental | 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. Receives: Drug: ION582 |
| Part 1 MAD: Cohort F | Experimental | ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 12 weeks between each dose administration. Receives: Drug: ION582 |
| Part 2 Group 1 | Experimental | ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals. Receives: Drug: ION582 |
| Part 2 Group 2 | Experimental | ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals. Receives: Drug: ION582 |
| Part 3 Group 1 | Experimental | ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals. Receives: Drug: ION582 |
| Part 3 Group 2 | Experimental | ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals. Receives: Drug: ION582 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
The safety and tolerability of ION582 will be assessed by determining the incidence, severity, and dose relationship of adverse effects and changes in the laboratory parameters by dose.
Measured: Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary outcomes (4)
Maximum Observed Plasma Concentration (Cmax) of ION582
Measured: Part 1: Up to Week 45; Part 2: Up to Week 81
Time to Reach Maximal Plasma Concentration (Tmax) of ION582
Measured: Part 1: Up to Week 45; Part 2: Up to Week 81
Plasma Elimination Half-Life (t1/2λz) of ION582
Measured: Part 1: Up to Week 45; Part 2: Up to Week 81
Concentration ION582 in CSF
Measured: Part 1: Up to Week 13; Part 2: Up to Week 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2021
- Study start22 Dec 2021
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05127226
- Sponsor's protocol ID
- ION582-CS1
- Other IDs
- 2021-003009-23
- Status last verified
- Aug 2026
- First submitted
- 9 Nov 2021
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome
- ClinicalTrials.gov ID
- NCT05127226
- Acronym / sponsor ID
- ION582-CS1
- Conditions
- Angelman Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Dec 2021 (actual)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 19 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part 1 MAD: Cohort A | Experimental | Drug: ION582ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. |
| Part 1 MAD: Cohort B | Experimental | Drug: ION582ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. |
| Part 1 MAD: Cohort C | Experimental | Drug: ION582ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. |
| Part 1 MAD: Cohort D | Experimental | Drug: ION582ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. |
| Part 1 MAD: Cohort E | Experimental | Drug: ION582ION582 will be administered as IT injection of over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. |
| Part 1 MAD: Cohort F | Experimental | Drug: ION582ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 12 weeks between each dose administration. |
| Part 2 Group 1 | Experimental | Drug: ION582ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals. |
| Part 2 Group 2 | Experimental | Drug: ION582ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals. |
| Part 3 Group 1 | Experimental | Drug: ION582ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals. |
| Part 3 Group 2 | Experimental | Drug: ION582ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals. |
Who may qualify
- Ages
- 0 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation)
- Male or female between the ages of 0-50 years of age, with signed informed consent from parent(s) or legal guardian(s)
- 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.
- 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 (4 listed)
- Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID).
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION582ION582 will be administered by IT injection. | Drug | Part 1 MAD: Cohort A, Part 1 MAD: Cohort B, Part 1 MAD: Cohort C, Part 1 MAD: Cohort D, Part 1 MAD: Cohort E, Part 1 MAD: Cohort F, Part 2 Group 1, Part 2 Group 2, Part 3 Group 1, Part 3 Group 2 |
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).
Time frame: Part 1: Up to Week 45; Part 2: Up to Week 81
The safety and tolerability of ION582 will be assessed by determining the incidence, severity, and dose relationship of adverse effects and changes in the laboratory parameters by dose.
4 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) of ION582
Time frame: Part 1: Up to Week 45; Part 2: Up to Week 81
Time to Reach Maximal Plasma Concentration (Tmax) of ION582
Time frame: Part 1: Up to Week 45; Part 2: Up to Week 81
Plasma Elimination Half-Life (t1/2λz) of ION582
Time frame: Part 1: Up to Week 45; Part 2: Up to Week 81
Concentration ION582 in CSF
Time frame: Part 1: Up to Week 13; Part 2: Up to Week 49
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Individual participant dataSharing planned: Yes. Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ION582 in people with Angelman Syndrome, run by Ionis Pharmaceuticals, Inc. at 11 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Australia, France, Israel, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: Part 1: Up to Week 45; Part 2: Up to Week 81). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.