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Trial record 1 of 1 for:    ionis | Angelman Syndrome
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HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05127226
Recruitment Status : Recruiting
First Posted : November 19, 2021
Last Update Posted : September 2, 2022
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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 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.

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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 : July 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety

Arm Intervention/treatment
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.




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

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, 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
Israel
Sheba Medical Center Recruiting
Ramat Gan, Israel, 5262100
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05127226    
Other Study ID Numbers: ION582-CS1
First Posted: November 19, 2021    Key Record Dates
Last Update Posted: September 2, 2022
Last Verified: August 2022
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