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

PHASE1PHASE2ACTIVE_NOT_RECRUITING

The purpose of this study is to evaluate the safety and tolerability of ascending doses of ION582 administered intrathecally in participants with Angelman syndrome.

Study details:

This is a Phase 1-2a, open-label study consisting of 3 parts in approximately 70 participants. Part 1 is a multiple ascending dose (MAD) study, consisting of a 13-week MAD Treatment Period and a minimum 12-week Post-MAD Follow-Up Period. Part 2 is a multi-center 49-week study where participants who completed Part 1 will receive IT bolus doses of ION582 followed by a minimum 12-week Part 2 follow up period.

Part 3 extends the treatment period for participants who completed Part 2 for up to an additional 3 years followed by a 32-week post-LTE follow up period.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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 0-50 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.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT05127226

Intervention or treatment

DRUG: ION582

Conditions

  • Angelman Syndrome

  • Condition: Angelman Syndrome

  • DRUG: ION582

  • Randwick, Australia

  • Sponsor: Ionis Pharmaceuticals, Inc.

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Sydney Children's Hospital, Kids Cancer Centre

Select from list below to view details:

  • Sydney Children's Hospital, Kids Cancer Centre

    Randwick, Australia

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Who is running the clinical trial?

IPI

Ionis Pharmaceuticals, Inc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/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
    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
      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
        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
          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
            EXPERIMENTAL: Part 1 MAD: Cohort F
            • ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 12 weeks between each dose administration.
            Drug: ION582
              EXPERIMENTAL: Part 2 Group 1
              • ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.
              Drug: ION582
                EXPERIMENTAL: Part 2 Group 2
                • ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.
                Drug: ION582
                  EXPERIMENTAL: Part 3 Group 1
                  • ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.
                  Drug: ION582
                    EXPERIMENTAL: Part 3 Group 2
                    • ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.
                    Drug: ION582

                      What is the study measuring?

                      Primary Outcome

                      MeasureDescriptionTime Frame
                      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.Part 1: Up to Week 45; Part 2: Up to Week 81

                      Secondary Outcome

                      MeasureDescriptionTime Frame
                      Maximum Observed Plasma Concentration (Cmax) of ION582Not SpecifiedPart 1: Up to Week 45; Part 2: Up to Week 81
                      Time to Reach Maximal Plasma Concentration (Tmax) of ION582Not SpecifiedPart 1: Up to Week 45; Part 2: Up to Week 81
                      Plasma Elimination Half-Life (t1/2λz) of ION582Not SpecifiedPart 1: Up to Week 45; Part 2: Up to Week 81
                      Concentration ION582 in CSFNot SpecifiedPart 1: Up to Week 13; Part 2: Up to Week 49
                      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
                      Claim this trial

                      References

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

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