2'-O-(2-METHOXYETHYL) MODIFIED ANTISENSE OLIGONUCLEOTIDE TARGETING UBE3A ANTISENSE TRANSCRIPT RNA for Angelman syndrome

Inclusion criteria

• {"criterion_text":"- Participant has a documented and certified diagnosis of Angelman syndrome (ubiquitin-protein ligase E3A deletion or UBE3A mutation)"}
• {"criterion_text":"- Male or female between the ages of 0-50 years of age, with signed informed consent from parent(s) or legal guardian(s)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Other protocol-defined inclusion criteria apply"}

Exclusion criteria

• {"criterion_text":"- Has documented molecular AS confirmation of paternal uniparental disomy or imprinting defect"}
• {"criterion_text":"- Any clinically significant 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"}
• {"criterion_text":"- 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). COVID-19 vaccinations are allowed."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Other protocol-defined exclusion criteria apply"}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Assessment based on incidence, severity, and dose-relationship of adverse effects and changes in laboratory parameters (safety and tolerability endpoints as stated)."}

Secondary endpoints

• {"endpoint_text":"- Maximum Observed Plasma Concentration of ION582","definition_or_measurement_approach":"Measurement of plasma concentration (Cmax) of ION582 as observed in sampled plasma."}
• {"endpoint_text":"- Time to Reach Maximal Plasma Concentration of ION582","definition_or_measurement_approach":"Measurement of time to observed maximal plasma concentration (Tmax) of ION582."}
• {"endpoint_text":"- Plasma Elimination Half-Life of ION582","definition_or_measurement_approach":"Determination of plasma elimination half-life (t1/2) of ION582 from plasma concentration–time data."}
• {"endpoint_text":"- Concentration ION582 in cerebrospinal fluid","definition_or_measurement_approach":"Measurement of ION582 concentration in cerebrospinal fluid (CSF)."}

France

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

19-08-2025

Processing Time Days

390

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

21-08-2025

Processing Time Days

392

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Ionis Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Sitero LLC

Responsibilities

code: 6

Name

PPD Development LP

Responsibilities

code: 8

Name

The Emmes Company LLC

Responsibilities

Angelman Syndrome Video Assessment (code: 15)

Name

WCG Clinical Inc.

Responsibilities

Rater Training (code: 15)

Name

Medpace Finland Oy

Responsibilities

Multiple operational roles (codes: 1,10,12,2,3,5,6,7,8)

Third parties

• {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"code: 6","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Sysnav","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"code: 15; ePRO questionnaires","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"The Emmes Company LLC","duties_or_roles":"code: 15; Angelman Syndrome Video Assessment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"code: 15; Rater Training","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes: 1,10,12,2,3,5,6,7,8","organisation_type":"Pharmaceutical company"}