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

Brief Title

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

Official Title

A Phase 1/2 Open-label, Multiple-dose, Dose-escalating Clinical Trial of the Safety and Tolerability of GTX-102 in Pediatric Patients With Angelman Syndrome (AS)

Brief 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.

Detailed Description

      This is a Phase 1/2, open-label, multiple-dose, study to evaluate the safety, tolerability,
      and plasma and CSF concentrations of GTX-102 in pediatric patients with AS.

      The study includes a monthly dosing period followed by a maintenance period. Eligible
      patients who meet all of the inclusion criteria and none of the exclusion criteria and who
      successfully complete all screening and baseline assessments will be assigned to one of 2
      dose cohorts based on patient age in Canada and UK; in the US all patients will enter a
      single dose cohort. GTX-102 will be administered by intrathecal (IT) injection via lumbar
      puncture (LP) at Baseline followed by 2-3 subsequent IT injections on study Days 30, 58 and
      86. The procedure for IT administration of GTX-102 will performed by a clinician with
      experience in LP and anesthetic care will be directed by experienced anesthesiologists with a
      focus on patient safety and comfort. The duration of study for each patient in the dose
      escalation phase is anticipated to be approximately 5 months. Patients will then transition
      to a maintenance phase of study where they may receive continued treatment with GTX-102.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Safety: incidence of adverse events

Secondary Outcome

 Pharmacokinetics of GTX-102


Angelman Syndrome



Study Arms / Comparison Groups

 GTX-102 Cohort 4
Description:  3.3 mg for 3-4 monthly doses followed by a quarterly maintenance regimen


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

February 24, 2020

Completion Date

January 24, 2023

Primary Completion Date

October 24, 2022

Eligibility 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

          -  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

          -  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




4 Years - 17 Years

Accepts Healthy Volunteers



Scott Stromatt, MD, 425-209-5817, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

GeneTX Biotherapeutics, LLC


 Ultragenyx Pharmaceutical Inc

Study Sponsor

Scott Stromatt, MD, Study Director, GeneTX Biotherapeutics, LLC

Verification Date

November 2021