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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05127226
Other study ID # ION582-CS1
Secondary ID 2021-003009-23
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date December 22, 2021
Est. completion date March 2029

Study information

Verified date March 2024
Source Ionis Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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 information / eligibility

Status Active, not recruiting
Enrollment 51
Est. completion date March 2029
Est. primary completion date March 2029
Accepts healthy volunteers No
Gender All
Age group 2 Years to 50 Years
Eligibility 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 completed. 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ION582
ION582 will be administered by IT injection.

Locations

Country Name City State
Australia Sydney Children's Hospital, Kids Cancer Centre Randwick
France Necker-Enfants Malades Hospital Paris
Israel Sheba Medical Center Ramat Gan
Italy Azienda Ospedaliera Universitaria Pisana Pisa
United Kingdom STRONG Group University of Oxford Oxford Oxfordshire
United States Colorado Children's Hospital Research Institute Aurora Colorado
United States Boston Children's Hospital Boston Massachusetts
United States University of North Carolina at Chapel Hill School of Medicine Carrboro North Carolina
United States Rush University Medical Center Chicago Illinois
United States Texas Children's Hospital Houston Texas
United States Rady Children's Hospital San Diego California

Sponsors (2)

Lead Sponsor Collaborator
Ionis Pharmaceuticals, Inc. Biogen

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Italy,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Maximum Observed Plasma Concentration (Cmax) of ION582 Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary Time to Reach Maximal Plasma Concentration (Tmax) of ION582 Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary Plasma Elimination Half-Life (t1/2?z) of ION582 Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary Concentration ION582 in CSF Part 1: Up to Week 13; Part 2: Up to Week 49
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