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

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)

The primary objective of the study is to evaluate the safety and tolerability of multiple-ascending doses of GTX-102 administered by intrathecal (IT) injection to participants with Angelman Syndrome (AS).

Study Overview

• Status: Completed
• Conditions: Angelman Syndrome
• Intervention / Treatment: Drug: GTX-102

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 participants with AS.

The study includes a Loading phase followed by a Maintenance phase. Participants may continue on GTX-102 during the Maintenance phase of the study until GTX-102 is commercially available, intolerable toxicity occurs, the parent/legal guardian withdraws consent, the participant enrolls in another experimental study, or this study is terminated.

This study was previously posted by GeneTX Biotherapeutics, LLC and was transferred to Ultragenyx in July 2022.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Brisbane, Australia, QLD 4101
    • Queensland Children's Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Parkville, Victoria, Australia, 3052
      • The Royal Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2E 7Z4
      • MAGIC Clinic Ltd
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H3V4
      • British Columbia Children's Hospital
  • Ontario
    • London, Ontario, Canada
      • Children's Hospital of Western Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada
      • McGill University Health Centre
• France
  • Marseille, France
    • Hôpital de la Timone
  • Paris, France, 75015
    • AP-HP Hopital Necker-Enfants Malades
• Germany
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig
• Israel
  • Ramat Gan, Israel
    • The Edmond and Lily Safra Children's Hospital
• Spain
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain
      • Hospital Sant Joan de Deu
    • Sabadell, Barcelona, Spain
      • Hospital Universitari Parc Tauli
  • Madrid
    • Majadahonda, Madrid, Spain
      • Hospital Universitario Puerta de Hierro
• United Kingdom
  • Cambridge, United Kingdom
    • Cambridge University Hospitals
  • London, United Kingdom
    • Great Ormond Street Hospital for Children
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • San Diego, California, United States, 92123
      • Rady Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent from parent(s) or legal guardian(s)
• Documented genetic confirmation of full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13 including class I, II or III
• Stable seizure control (defined as clinically stable with no changes in antiepileptic medications over the prior 1 month before the screening visit, other than weight associated dose adjustments)
• Able to ambulate independently, or with an assistive device (note, a child whose primary means of mobility is by wheelchair is excluded from the study)
• Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time within 1.2 x the normal limits
• Normal renal function with serum creatinine and spot urine protein ≤ 1.4 x the upper limit of normal (ULN)
• Normal hepatic function with total bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≤ 1.4 x ULN. Exception: levels ≤ 2 × ULN are acceptable if due to anti-epileptic drugs (AEDs) or Gilbert syndrome
• Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures, including LP procedure
• Able to tolerate the anesthetic regimen, if required for LP procedure
• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Female of non-childbearing potential (ie, pre-menarche), Female of childbearing potential who agrees to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 3 months after the final dose of GTX-102
• A male patient is eligible to participate if he agrees to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 3 months after the final dose of GTX-102

Exclusion Criteria:

• Any change in medications (excluding AEDs) or diet/supplements intended to treat symptoms of AS (eg, sleeping aids, supplements, dietary change including ketogenic or low-glycemic index diet, other) over the prior 1 month before screening
• Any bleeding or platelet disorder
• Any clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurological, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, 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
• Known positive for hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
• 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 (eg, heparin, low molecular weight heparin, platelet inhibitors)
• Any prior use of gene therapy
• Use of any investigational drugs in the past 6 months or within 5 half-lives, whichever period is greater (with the exception of prior GTX 102)
• Known hypersensitivity to any oligonucleotide, as demonstrated by an immune mediated reaction (eg, pneumonitis, hepatitis, nephritis, neuritis, or other system inflammation), or a systemic allergic reaction such as signs and symptoms of anaphylaxis, urticaria, clinically significant rash
• Patient is pregnant or lactating
• Any medical condition that would require intubation for the anesthesia procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GTX-102 Cohort 1; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort 2; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort 3; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort 4; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort 5; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort 6; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort 7; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort US; 2 mg for 4 monthly doses followed by a quarterly maintenance regimen	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Expanded Enrollment Cohort A; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Expanded Enrollment Cohort B; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Expanded Enrollment Cohort C; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Expanded Enrollment Cohort D; 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)	Drug: GTX-102; antisense oligonucleotide
Experimental: GTX-102 Cohort E; 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)	Drug: GTX-102; antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), Adverse Events of Special Interest (AESIs), AEs Leading to Discontinuation and Severity of AEs	Up to Day 337

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of GTX-102 over time	Maximum drug concentration (Cmax)	Up to Day 337

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

General Publications

• Dindot SV, Christian S, Murphy WJ, Berent A, Panagoulias J, Schlafer A, Ballard J, Radeva K, Robinson R, Myers L, Jepp T, Shaheen H, Hillman P, Konganti K, Hillhouse A, Bredemeyer KR, Black L, Douville J; FIRE consortium; FIRE Consortium. An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the UBE3A-AS transcript. Sci Transl Med. 2023 Mar 22;15(688):eabf4077. doi: 10.1126/scitranslmed.abf4077. Epub 2023 Mar 22.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): January 8, 2025
• Study Completion (Actual): January 8, 2025

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Imprinting Disorders; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital Abnormalities; Movement Disorders; Abnormalities, Multiple; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Angelman Syndrome
• Other Study ID Numbers: GTX-102-001; 2021-001793-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No