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

NCT05127226 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ION582-CS12021-003009-23
• Study Type: interventional
• Target: 70
• Locations: 6 countries
• Sites: 11

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.

Conditions

Angelman Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  Part 1: Up to Week 45; Part 2: Up to Week 81

Secondary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) of ION582

  Part 1: Up to Week 45; Part 2: Up to Week 81

• Time to Reach Maximal Plasma Concentration (Tmax) of ION582

  Part 1: Up to Week 45; Part 2: Up to Week 81

• Plasma Elimination Half-Life (t1/2λz) of ION582

  Part 1: Up to Week 45; Part 2: Up to Week 81

• Concentration ION582 in CSF

  Part 1: Up to Week 13; Part 2: Up to Week 49

Study Arms (10)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: ION582

Interventions

ION582 DRUG

ION582 will be administered by IT injection.

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

Eligibility Criteria

• Age: 0 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (11)

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Colorado Children's Hospital Research Institute

Aurora, Colorado, 80045, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

University of North Carolina at Chapel Hill School of Medicine

Carrboro, North Carolina, 27510, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Sydney Children's Hospital, Kids Cancer Centre

Randwick, NSW 2031, Australia

ACTIVE NOT RECRUITING

Necker-Enfants Malades Hospital

Paris, 75015, France

RECRUITING

Sheba Medical Center

Ramat Gan, 5262100, Israel

RECRUITING

Azienda Ospedaliera Universitaria Pisana

Pisa, 56126, Italy

RECRUITING

STRONG Group University of Oxford

Oxford, Oxfordshire, OX3 9DU, United Kingdom

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Angelman Syndrome

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Central Study Contacts

Ionis Pharmaceuticals

CONTACT

(844) 200-6263; IonisAngelmanStudy@clinicaltrialmedia.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: November 19, 2021
• Study Start: December 22, 2021
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

FR (1); GB (1); US (6); AU (1); IL (1); IT (1)