ClinicalTrials.gov

History of Changes for Study: NCT05127226
HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
Latest version (submitted March 19, 2024) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 November 9, 2021 None (earliest Version on record)
2 December 22, 2021 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 January 7, 2022 Study Status and Contacts/Locations
4 January 14, 2022 Contacts/Locations and Study Status
5 February 15, 2022 Study Status and Contacts/Locations
6 April 4, 2022 Study Status and Contacts/Locations
7 July 25, 2022 Study Status and Contacts/Locations
8 August 2, 2022 Study Status and Contacts/Locations
9 August 31, 2022 Contacts/Locations and Study Status
10 October 13, 2022 Study Status and Contacts/Locations
11 January 6, 2023 Study Status, Arms and Interventions, Outcome Measures, Contacts/Locations, Study Description, Sponsor/Collaborators and Study Identification
12 February 15, 2023 Study Status and Contacts/Locations
13 March 24, 2023 Study Status and Contacts/Locations
14 May 24, 2023 Study Status and Contacts/Locations
15 December 7, 2023 Recruitment Status, Study Status, Contacts/Locations and Study Design
16 March 19, 2024 Study Status, Arms and Interventions and Study Description
Comparison Format:

Scroll up to access the controls

Study NCT05127226
Submitted Date:  November 9, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: ION582-CS1
Brief Title: HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
Official Title: HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2021
Overall Status: Not yet recruiting
Study Start: November 2021
Primary Completion: July 2023 [Anticipated]
Study Completion: December 2023 [Anticipated]
First Submitted: November 9, 2021
First Submitted that
Met QC Criteria:
November 9, 2021
First Posted: November 19, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
November 9, 2021
Last Update Posted: November 19, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Ionis Pharmaceuticals, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief 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.
Detailed Description: This is a Phase 1-2a, open-label dose-escalation study of ION582 enrolling up to approximately 44 participants. Following a screening period of up to 4 weeks, eligible participants will receive intrathecal (IT) injections of ION582. Participants will be followed for up to 32 weeks after dosing.
Open or close this module Conditions
Conditions: Angelman Syndrome
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Number of Arms: 5
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 44 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort A: Dose 1
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
Drug: ION582
ION582 will be administered by IT injection.
Experimental: Cohort B: Dose 2
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
Drug: ION582
ION582 will be administered by IT injection.
Experimental: Cohort C: Dose 3
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
Drug: ION582
ION582 will be administered by IT injection.
Experimental: Cohort D: Dose TBD
ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.
Drug: ION582
ION582 will be administered by IT injection.
Experimental: Cohort E: Dose TBD
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.
Drug: ION582
ION582 will be administered by IT injection.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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: From Baseline up to 47 weeks ]

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.
Secondary Outcome Measures:
1. Maximum Observed Plasma Concentration (Cmax) of ION582
[ Time Frame: Over weeks 1-47 ]

2. Time to Reach Maximal Plasma Concentration (Tmax) of ION582
[ Time Frame: Over weeks 1-47 ]

3. Plasma Elimination Half-Life (t1/2λz) of ION582
[ Time Frame: Over weeks 1-47 ]

4. Concentration ION582 in CSF
[ Time Frame: Over weeks 1-13 ]

Open or close this module Eligibility
Minimum Age: 2 Years
Maximum Age: 50 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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.
Open or close this module Contacts/Locations
Central Contact Person: Ionis Pharmaceuticals
Telephone: 800-679-4747
Email: patients@ionisph.com
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services