HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
- Registration Number
- NCT05127226
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- 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 study consisting of 3 parts. Part 1 is a multiple ascending dose (MAD) study, consisting of a 13-week MAD Treatment Period and a minimum 12-week but up to 32-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 will enroll approximately 44, and up to 55, participants.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 51
- 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 2-50 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 3 Group 1 ION582 ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals. Part 1 MAD: Cohort B ION582 ION582 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 ION582 ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration. Part 2 Group 1 ION582 ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals. Part 3 Group 2 ION582 ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals. Part 2 Group 2 ION582 ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals. Part 1 MAD: Cohort C ION582 ION582 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 A ION582 ION582 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 ION582 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.
- Primary Outcome Measures
Name Time Method 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). 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.
- Secondary Outcome Measures
Name Time Method Time to Reach Maximal Plasma Concentration (Tmax) of ION582 Part 1: Up to Week 45; Part 2: Up to Week 81 Maximum Observed Plasma Concentration (Cmax) 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
Related Research Topics
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Trial Locations
- Locations (11)
Rady Children's Hospital
🇺🇸San Diego, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of North Carolina at Chapel Hill School of Medicine
🇺🇸Carrboro, North Carolina, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Sydney Children's Hospital, Kids Cancer Centre
🇦🇺Randwick, Australia
Necker-Enfants Malades Hospital
🇫🇷Paris, France
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Colorado Children's Hospital Research Institute
🇺🇸Aurora, Colorado, United States
Sheba Medical Center
🇮🇱Ramat Gan, Israel
STRONG Group University of Oxford
🇬🇧Oxford, Oxfordshire, United Kingdom
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Italy