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

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ClinicalTrials.gov Identifier: NCT05127226
Recruitment Status : Recruiting
First Posted : November 19, 2021
Last Update Posted : May 26, 2023
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Angelman Syndrome Drug: ION582 Phase 1 Phase 2

Detailed Description:
This is a Phase 1-2a, open-label study consisting of 2 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 the Long-Term Extension (LTE) Period including a 49-week LTE Treatment Period, where participants who completed Part 1 will receive IT bolus doses of ION582 and a 32-week Post-LTE Follow-Up Period. The study will enroll approximately 44, and up to 55 participants.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: HALOS: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients With Angelman Syndrome
Actual Study Start Date : December 22, 2021
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety

Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: ION582
ION582 will be administered by IT injection.
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.
 Drug: ION582
ION582 will be administered by IT injection.
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.
 Drug: ION582
ION582 will be administered by IT injection.
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.
 Drug: ION582
ION582 will be administered by IT injection.
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.
 Drug: ION582
ION582 will be administered by IT injection.
Experimental: Part 2 LTE: Group 1
ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.
 Drug: ION582
ION582 will be administered by IT injection.
Experimental: Part 2 LTE: Group 2
ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.
 Drug: ION582
ION582 will be administered by IT injection.


Outcome Measures
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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: Part 1: Up to Week 45; Part 2: Up to Week 81 ]
    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: Part 1: Up to Week 45; Part 2: Up to Week 81 ]
  2. Time to Reach Maximal Plasma Concentration (Tmax) of ION582 [ Time Frame: Part 1: Up to Week 45; Part 2: Up to Week 81 ]
  3. Plasma Elimination Half-Life (t1/2λz) of ION582 [ Time Frame: Part 1: Up to Week 45; Part 2: Up to Week 81 ]
  4. Concentration ION582 in CSF [ Time Frame: Part 1: Up to Week 13; Part 2: Up to Week 49 ]

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05127226


Contacts
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Contact: Ionis Pharmaceuticals (844) 979-3914 IonisAngelmanStudy@clinicaltrialmedia.com

Locations
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United States, California
Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
United States, Colorado
Colorado Children's Hospital Research Institute Recruiting
Aurora, Colorado, United States, 80045
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02215
United States, North Carolina
University of North Carolina at Chapel Hill School of Medicine Recruiting
Carrboro, North Carolina, United States, 27510
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Australia
Sydney Children's Hospital, Kids Cancer Centre Recruiting
Randwick, Australia, NSW 2031
France
Necker-Enfants Malades Hospital Recruiting
Paris, France, 75015
Israel
Sheba Medical Center Recruiting
Ramat Gan, Israel, 5262100
Italy
Azienda Ospedaliera Universitaria Pisana Recruiting
Pisa, Italy, 56126
United Kingdom
STRONG Group University of Oxford Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Biogen
More Information
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05127226    
Other Study ID Numbers: ION582-CS1
2021-003009-23 ( EudraCT Number )
First Posted: November 19, 2021    Key Record Dates
Last Update Posted: May 26, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Angelman Syndrome
Syndrome
Disease
Pathologic Processes
Movement Disorders
Central Nervous System Diseases
 Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn