- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05127226
HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
March 19, 2024 updated by: Ionis Pharmaceuticals, Inc.
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
51
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Ionis Pharmaceuticals
- Phone Number: (844) 979-3914
- Email: IonisAngelmanStudy@clinicaltrialmedia.com
Study Locations
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Randwick, Australia, NSW 2031
- Sydney Children's Hospital, Kids Cancer Centre
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Paris, France, 75015
- Necker-Enfants Malades Hospital
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Ramat Gan, Israel, 5262100
- Sheba Medical Center
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Pisa, Italy, 56126
- Azienda Ospedaliera Universitaria Pisana
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Oxfordshire
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Oxford, Oxfordshire, United Kingdom, OX3 9DU
- STRONG Group University of Oxford
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California
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San Diego, California, United States, 92123
- Rady Children's Hospital
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Colorado
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Aurora, Colorado, United States, 80045
- Colorado Children's Hospital Research Institute
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Illinois
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Chicago, Illinois, United States, 60612
- Rush University Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Boston Children's Hospital
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North Carolina
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Carrboro, North Carolina, United States, 27510
- University of North Carolina at Chapel Hill School of Medicine
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Texas
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Houston, Texas, United States, 77030
- Texas Children's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 50 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part 1 MAD: Cohort A
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
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ION582 will be administered by IT injection.
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Experimental: Part 1 MAD: Cohort B
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
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ION582 will be administered by IT injection.
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Experimental: Part 1 MAD: Cohort C
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
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ION582 will be administered by IT injection.
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Experimental: Part 1 MAD: Cohort D
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
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ION582 will be administered by IT injection.
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Experimental: Part 1 MAD: Cohort E
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.
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ION582 will be administered by IT injection.
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Experimental: Part 2 Group 1
ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.
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ION582 will be administered by IT injection.
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Experimental: Part 2 Group 2
ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.
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ION582 will be administered by IT injection.
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Experimental: Part 3 Group 1
ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.
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ION582 will be administered by IT injection.
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Experimental: Part 3 Group 2
ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.
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ION582 will be administered by IT injection.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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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.
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Part 1: Up to Week 45; Part 2: Up to Week 81
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Maximum Observed Plasma Concentration (Cmax) of ION582
Time Frame: Part 1: Up to Week 45; Part 2: Up to Week 81
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Part 1: Up to Week 45; Part 2: Up to Week 81
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Time to Reach Maximal Plasma Concentration (Tmax) of ION582
Time Frame: Part 1: Up to Week 45; Part 2: Up to Week 81
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Part 1: Up to Week 45; Part 2: Up to Week 81
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Plasma Elimination Half-Life (t1/2λz) of ION582
Time Frame: Part 1: Up to Week 45; Part 2: Up to Week 81
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Part 1: Up to Week 45; Part 2: Up to Week 81
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Concentration ION582 in CSF
Time Frame: Part 1: Up to Week 13; Part 2: Up to Week 49
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Part 1: Up to Week 13; Part 2: Up to Week 49
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 22, 2021
Primary Completion (Estimated)
March 1, 2029
Study Completion (Estimated)
March 1, 2029
Study Registration Dates
First Submitted
November 9, 2021
First Submitted That Met QC Criteria
November 9, 2021
First Posted (Actual)
November 19, 2021
Study Record Updates
Last Update Posted (Actual)
March 20, 2024
Last Update Submitted That Met QC Criteria
March 19, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ION582-CS1
- 2021-003009-23 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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