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

Primary Purpose

Angelman Syndrome

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

ION582

About this trial

This is an interventional treatment trial for Angelman Syndrome

Eligibility Criteria

2 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation)
Male or female between the ages of 2-50 years of age, with signed informed consent from parent(s) or legal guardian(s)
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.
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:

Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID).
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.
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.
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.

Sites / Locations

Rady Children's HospitalRecruiting
Colorado Children's Hospital Research InstituteRecruiting
Rush University Medical CenterRecruiting
Boston Children's HospitalRecruiting
University of North Carolina at Chapel Hill School of MedicineRecruiting
Texas Children's HospitalRecruiting
Sydney Children's Hospital, Kids Cancer CentreRecruiting
Necker-Enfants Malades HospitalRecruiting
Sheba Medical CenterRecruiting
Azienda Ospedaliera Universitaria PisanaRecruiting
STRONG Group University of OxfordRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Part 1 MAD: Cohort A

Part 1 MAD: Cohort B

Part 1 MAD: Cohort C

Part 1 MAD: Cohort D

Part 1 MAD: Cohort E

Part 2 LTE: Group 1

Part 2 LTE: Group 2

Arm Description

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

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.

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of ION582

Time to Reach Maximal Plasma Concentration (Tmax) of ION582

Plasma Elimination Half-Life (t1/2λz) of ION582

Concentration ION582 in CSF

Full Information

NCT ID

NCT05127226

First Posted

November 9, 2021

Last Updated

May 24, 2023

Sponsor

Ionis Pharmaceuticals, Inc.

Collaborators

Biogen

1. Study Identification

Unique Protocol Identification Number

NCT05127226

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 22, 2021 (Actual)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ionis Pharmaceuticals, Inc.

Collaborators

Biogen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Angelman Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1 MAD: Cohort A

Arm Type

Experimental

Arm Description

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Arm Title

Part 1 MAD: Cohort B

Arm Type

Experimental

Arm Description

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Arm Title

Part 1 MAD: Cohort C

Arm Type

Experimental

Arm Description

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Arm Title

Part 1 MAD: Cohort D

Arm Type

Experimental

Arm Description

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Arm Title

Part 1 MAD: Cohort E

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2 LTE: Group 1

Arm Type

Experimental

Arm Description

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Arm Title

Part 2 LTE: Group 2

Arm Type

Experimental

Arm Description

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Intervention Type

Drug

Intervention Name(s)

ION582

Intervention Description

ION582 will be administered by IT injection.

Primary Outcome Measure Information:

Title

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).

Description

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.

Time Frame

Part 1: Up to Week 45; Part 2: Up to Week 81

Secondary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax) of ION582

Time Frame

Part 1: Up to Week 45; Part 2: Up to Week 81

Title

Time to Reach Maximal Plasma Concentration (Tmax) of ION582

Time Frame

Part 1: Up to Week 45; Part 2: Up to Week 81

Title

Plasma Elimination Half-Life (t1/2λz) of ION582

Time Frame

Part 1: Up to Week 45; Part 2: Up to Week 81

Title

Concentration ION582 in CSF

Time Frame

Part 1: Up to Week 13; Part 2: Up to Week 49

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation) Male or female between the ages of 2-50 years of age, with signed informed consent from parent(s) or legal guardian(s) 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. 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: Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID). 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. 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ionis Pharmaceuticals

Phone

(844) 979-3914

IonisAngelmanStudy@clinicaltrialmedia.com

Facility Information:

Facility Name

Rady Children's Hospital

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Individual Site Status

Recruiting

Facility Name

Colorado Children's Hospital Research Institute

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Individual Site Status

Recruiting

Facility Name

Rush University Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Individual Site Status

Recruiting

Facility Name

Boston Children's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Individual Site Status

Recruiting

Facility Name

University of North Carolina at Chapel Hill School of Medicine

City

Carrboro

State/Province

North Carolina

ZIP/Postal Code

27510

Country

United States

Individual Site Status

Recruiting

Facility Name

Texas Children's Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Name

Sydney Children's Hospital, Kids Cancer Centre

City

Randwick

ZIP/Postal Code

NSW 2031

Country

Australia

Individual Site Status

Recruiting

Facility Name

Necker-Enfants Malades Hospital

City

Paris

ZIP/Postal Code

75015

Country

France

Individual Site Status

Recruiting

Facility Name

Sheba Medical Center

City

Ramat Gan

ZIP/Postal Code

5262100

Country

Israel

Individual Site Status

Recruiting

Facility Name

Azienda Ospedaliera Universitaria Pisana

City

Pisa

ZIP/Postal Code

56126

Country

Italy

Individual Site Status

Recruiting

Facility Name

STRONG Group University of Oxford

City

Oxford

State/Province

Oxfordshire

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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