What is the mechanism of action of this treatment?

The most common treatments for Angelman Syndrome (AS) often target the underlying genetic and neurological dysfunctions associated with the disorder. GTX-102, for example, is administered via intrathecal injection to directly deliver therapeutic agents to the central nervous system, aiming to modulate the expression of the UBE3A gene, which is typically deficient in AS patients. This targeted approach is crucial as it addresses the root cause of AS at the molecular level, potentially improving neurological function and reducing symptoms such as seizures, motor difficulties, and cognitive impairments. Ensuring the safety and tolerability of such treatments is vital to minimize adverse effects and enhance the quality of life for AS patients.

What side effects are associated with this type of intervention?

The most common treatments for Angelman Syndrome, particularly those involving intrathecal injections like GTX-102, often focus on managing symptoms and improving quality of life. Known side effects of such treatments can include mild to moderate adverse reactions at the injection site, such as pain, swelling, or redness. Systemic side effects may include headache, nausea, dizziness, and, in some cases, more severe neurological effects. It is crucial to monitor patients closely to manage and mitigate these side effects effectively.

What prior FDA approvals exist?

As of now, there are no FDA-approved drugs specifically for the treatment of Angelman Syndrome. Current management primarily focuses on symptomatic treatments, such as antiepileptic drugs for seizures, physical therapy, and behavioral interventions. GTX-102, being studied for its safety and tolerability when administered intrathecally, represents a novel approach targeting the underlying genetic mechanisms of the syndrome. This investigational treatment aims to address the root cause rather than just the symptoms, which is a significant shift from existing therapeutic strategies.

What other types of research exist?

As of 2024, promising novel alternatives to GTX-102 for Angelman Syndrome patients include gene therapy approaches such as antisense oligonucleotides (ASOs) targeting the UBE3A gene, and CRISPR-based gene editing techniques. These therapies aim to reactivate the paternal allele of the UBE3A gene, potentially offering more effective and long-lasting benefits compared to traditional treatments.

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GTX-102 for Angelman Syndrome (KIK-AS Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by GeneTX Biotherapeutics, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented genetic confirmation of full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13 including class I, II or III

Normal renal function with serum creatinine and spot urine protein ≤ 1.4 x the upper limit of normal (ULN)

Must not have

Any bleeding or platelet disorder

Drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to day 337

Awards & highlights

Summary

This trial is testing a new drug called GTX-102, which is given directly into the spinal fluid. It aims to help children with Angelman Syndrome, a genetic disorder affecting the nervous system. The study will check if the drug is safe and how it behaves in the body.

Who is the study for?

This trial is for children with Angelman Syndrome confirmed by genetic testing, who have stable seizure control and can walk independently or with help. They must not be wheelchair-bound, have normal blood clotting and organ function tests, agree to follow study procedures including lumbar puncture (spinal tap), and use contraception if of childbearing age.

What is being tested?

The trial studies the safety of multiple doses of GTX-102 given through spinal injections in kids with Angelman Syndrome. It aims to see how well participants tolerate this treatment over time.

What are the potential side effects?

While specific side effects are not listed here, common risks may include discomfort at the injection site, potential allergic reactions to GTX-102 or anesthesia used during lumbar punctures, and general risks associated with intrathecal injections such as headache or back pain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My AS is caused by a complete UBE3A gene deletion from my mother.

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My kidney function is normal, with acceptable creatinine and protein levels.

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I can walk on my own or with help from a device.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a bleeding or platelet disorder.

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I am not taking medications that increase bleeding risk.

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I have previously undergone gene therapy.

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I currently have an active infection.

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I have a condition that could make a spinal tap risky or difficult.

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I need a breathing tube for anesthesia due to a medical condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to day 337

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to day 337

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to day 337 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Pharmacokinetics of GTX-102 over time

Other study objectives

Exploratory: Adaptive behaviors

Exploratory: Change in communication

Exploratory: Change in development

+5 more

Trial Design

13Treatment groups

Experimental Treatment

Group I: GTX-102 Expanded Enrollment Cohort DExperimental Treatment1 Intervention

Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants ≥ 8 to 17 years of age)

Group II: GTX-102 Expanded Enrollment Cohort CExperimental Treatment1 Intervention

Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants 4 to \<8 years of age)

Group III: GTX-102 Expanded Enrollment Cohort BExperimental Treatment1 Intervention

Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age)

Group IV: GTX-102 Expanded Enrollment Cohort AExperimental Treatment1 Intervention

Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants 4 to \<8 years of age)

Group V: GTX-102 Cohort USExperimental Treatment1 Intervention

2 mg for 4 monthly doses followed by a quarterly maintenance regimen

Group VI: GTX-102 Cohort EExperimental Treatment1 Intervention

Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in participants that transition from GTX-102 US Cohort only)

Group VII: GTX-102 Cohort 7Experimental Treatment1 Intervention

10 mg starting dose followed by slow intra-patient dose escalation up to 12 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age)

Group VIII: GTX-102 Cohort 6Experimental Treatment1 Intervention

7.5 mg starting dose followed by slow intra-patient dose escalation up to 10 mg and then a maintenance phase (in Ex-U.S participants 4 to \<8 years of age)

Group IX: GTX-102 Cohort 5Experimental Treatment1 Intervention

5 mg starting dose followed by slow intra-patient dose escalation up to 7.5 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age)

Group X: GTX-102 Cohort 4Experimental Treatment1 Intervention

3.3 mg starting dose followed by slow intra-patient dose escalation up to 5 mg and then a maintenance phase (in Ex-U.S participants 4 to \<8 years of age)

Group XI: GTX-102 Cohort 3Experimental Treatment1 Intervention

20 mg starting dose followed by intra-patient dose escalation up to 55 mg and then a maintenance phase (in U.S participants 4 to \<17 years of age)

Group XII: GTX-102 Cohort 2Experimental Treatment1 Intervention

10 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to \<17 years of age)

Group XIII: GTX-102 Cohort 1Experimental Treatment1 Intervention

3.3 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to \<17 years of age)

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Angelman Syndrome (AS) often target the underlying genetic and neurological dysfunctions associated with the disorder. GTX-102, for example, is administered via intrathecal injection to directly deliver therapeutic agents to the central nervous system, aiming to modulate the expression of the UBE3A gene, which is typically deficient in AS patients. This targeted approach is crucial as it addresses the root cause of AS at the molecular level, potentially improving neurological function and reducing symptoms such as seizures, motor difficulties, and cognitive impairments. Ensuring the safety and tolerability of such treatments is vital to minimize adverse effects and enhance the quality of life for AS patients.

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