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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05127226




Registration number
NCT05127226
Ethics application status
Date submitted
9/11/2021
Date registered
19/11/2021

Titles & IDs
Public title
HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
Scientific title
HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome
Secondary ID [1] 0 0
2021-003009-23
Secondary ID [2] 0 0
ION582-CS1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Angelman Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ION582

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.

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.

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.

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.

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.

Experimental: Part 2 Group 1 - ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Experimental: Part 2 Group 2 - ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Experimental: Part 3 Group 1 - ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.

Experimental: Part 3 Group 2 - ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.


Treatment: Drugs: ION582
ION582 will be administered by IT injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary outcome [1] 0 0
Maximum Observed Plasma Concentration (Cmax) of ION582
Timepoint [1] 0 0
Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary outcome [2] 0 0
Time to Reach Maximal Plasma Concentration (Tmax) of ION582
Timepoint [2] 0 0
Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary outcome [3] 0 0
Plasma Elimination Half-Life (t1/2?z) of ION582
Timepoint [3] 0 0
Part 1: Up to Week 45; Part 2: Up to Week 81
Secondary outcome [4] 0 0
Concentration ION582 in CSF
Timepoint [4] 0 0
Part 1: Up to Week 13; Part 2: Up to Week 49

Eligibility
Key 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.
Minimum age
2 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2029
Actual
Sample size
Target
Accrual to date
Final
51
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sydney Children's Hospital, Kids Cancer Centre - Randwick
Recruitment postcode(s) [1] 0 0
NSW 2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Israel
State/province [8] 0 0
Ramat Gan
Country [9] 0 0
Italy
State/province [9] 0 0
Pisa
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Oxfordshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ionis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05127226