A Study Testing the Safety and How Well GTX-102 Works in Adults and Children with Angelman Syndrome

Initial treatment period

The study medication GTX-102 (apazunersen) will be administered directly into the spinal fluid through a procedure called intrathecal injection. This means the medication is delivered into the space surrounding the spinal cord using a needle inserted into the lower back.

A solution called GTX/UX Diluent and Flush Solution will also be used during the procedure. This solution contains sodium dihydrogen phosphate dihydrate, disodium phosphate, potassium chloride, sodium chloride, calcium chloride dihydrate, and magnesium sulfate heptahydrate.

The treatment will be administered through a procedure similar to a lumbar puncture. Anesthesia will be provided during the procedure, but intubation (insertion of a breathing tube) will not be required.

Before each dose, premedication may be given to help with the procedure.

Regular assessments and monitoring

Throughout the study, various assessments will be conducted to monitor safety and measure changes in symptoms.

Safety monitoring will include checking for any adverse events (unwanted side effects) and serious adverse events (more severe side effects). The frequency, severity, and relationship of these events to the study medication, procedure, or premedication will be recorded.

Laboratory tests will be performed regularly, including blood tests to check clotting factors and platelet counts.

Imaging studies using MRI (magnetic resonance imaging) will be performed at scheduled intervals. This is a scan that uses magnets and radio waves to create detailed pictures of the inside of the body.

Developmental and behavioral assessments

Depending on age and specific diagnosis type, different assessments will be performed to evaluate progress.

For younger children (ages 1 to under 4 years with deletion-type diagnosis), assessments will focus on cognitive abilities, communication skills, and gross motor function (large body movements like walking and sitting).

For children ages 4 to under 18 years, assessments will evaluate cognitive abilities, communication skills (both understanding and expressing language), behavior patterns including hyperactivity and noncompliance, sleep quality, and motor function.

For adults ages 18 to under 65 years, assessments will focus on communication skills (both understanding and expressing language), behavior patterns including irritability, and motor function.

These assessments will be conducted at baseline (before treatment starts) and at day 338 (approximately 11 months after starting treatment).

Key evaluation timepoint

The primary evaluation will occur at day 338 after starting treatment.

At this timepoint, changes from baseline will be measured across multiple areas depending on the specific subprotocol.

The assessments may include measures of thinking abilities, understanding language, expressing language, behavior challenges, sleep patterns, and movement abilities.

A multidomain responder index (MDRI) may be calculated, which combines results from multiple assessment areas to provide an overall measure of response to treatment.

Contraception requirements during study participation

If applicable, females of childbearing potential who are sexually active must use highly effective contraception or practice abstinence from the time of informed consent through at least 6 months after the final dose of study medication.

Males who are sexually active must remain abstinent or use acceptable contraceptive methods during the study and for at least 3 months after the final dose of study medication.

Study completion

The study is expected to continue until approximately January 2030.

Follow-up assessments will continue after the primary evaluation timepoint to monitor long-term safety and effects of the treatment.

All scheduled visits, procedures, and assessments must be completed as planned throughout the duration of participation in the study.