A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome

• Status: Recruiting
• Trial end date: 2023-01-24
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1/2, open-label, multiple-dose, study to evaluate the safety, tolerability, and plasma and cerebrospinal fluid (CSF) concentrations of GTX-102 in pediatric patients with Angelman syndrome. Up to 20 patients (male and female) ≥ 4 and ≤ 17 years of age with a genetically confirmed diagnosis of full maternal UBE3A gene deletion (within 15q11.2-q13 region) will be enrolled.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GeneTx Biotherapeuics, LLC.; GeneTX Biotherapeutics, LLC
• Collaborator: Ultragenyx Pharmaceutical Inc

Criteria

Inclusion Criteria:

• Signed informed consent from parent(s) or legal guardian(s)

• Documented genetic confirmation of full maternal UBE3A gene deletion causing AS (e.g. DNA methylation testing with either a chromosomal microarray or FISH) in the region of 15q11.2-q13 including class I, II or III).

• Age ≥ 4 to ≤ 17 years at screening (in US Age ≥ 4 to < 8 years at screening)

• Stable seizure control (defined as clinically stable with no changes in antiepileptic medications over the prior 1 month before screening visit, other than weight associated dose adjustments)

• Platelet count, prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits

• Normal renal function with serum creatinine and spot urine protein within normal limits

• Normal hepatic function with total bilirubin, aspartate aminotransferase (AST),alanine aminotransferase (ALT) and alkaline phosphatase within normal limits

• Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures LP.

• Able to tolerate the anesthetic regimen required for LP procedure

Exclusion Criteria:

• Any change in medications (excluding antiepileptic drugs) or diet intended to treat symptoms of AS (e.g. sleeping aids, supplements, ketogenic or low-glycemic index diet, other) over the prior 3 months before screening.

• Inability to ambulate independently or with an assistive device or caregiver hand-hold

• Any bleeding or platelet disorder

• 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.

• Any laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study result

• Any active infection

• Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture

• Drugs that increase the risk of bleeding (e.g. heparin, low molecular weight heparin, platelet inhibitors).

• Use of any investigational oligonucleotide in the past 6 months

• Any prior use of gene therapy

• Use of any investigational drugs in the past 6 months

• Any medical condition that would require intubation for the anesthesia procedure