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

Angelman Syndrome Clinical Trial

Official title:

HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome

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
• Start date: December 22, 2021
• Est. completion date: March 2029

Study information

• Verified date: June 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• 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.

Related Conditions & MeSH terms

• Angelman Syndrome
• Syndrome

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 (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

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