Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With Angelman Syndrome (AS) (Aspire)

A Phase 3, Randomized, Double-blind, Sham-controlled Study Investigating the Efficacy and Safety of GTX-102 in Pediatric Subjects With Angelman Syndrome

The primary objective of this study is to evaluate the effect of GTX-102 in cognitive function in participants with deletion-type Angelman Syndrome (AS).

Study Overview

• Status: Active, not recruiting
• Conditions: Angelman Syndrome
• Intervention / Treatment: Drug: GTX-102; Procedure: Sham-LP

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Vancouver, Canada, V6H 3V4
    • British Columbia Children's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A3J1
      • McGill University Health Centre
• Germany
  • Hamburg, Germany, 20251
    • Universitaetsklinikum Hamburg-Eppendorf
  • Leipzig, Germany, 04155
    • University of Leipzig
  • Munich, Germany, 80336
    • Haunersche Kinderklinik
• Japan
  • Osaka, Japan, 543-0021
    • Osaka City General Hospital
  • Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 467-0001
      • Nagoya City University Graduate School of Medical Sciences
• Poland
  • Gdansk, Poland, 80211
    • Medical University of Gdansk
  • Lodz, Poland, 93-338
    • Polish Mothers Memorial Institute
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Déu
  • Barcelona, Spain, 08208
    • Hospital Universitario Parc Taulí
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai
    • San Diego, California, United States, 92123
      • UCSD, Rady Children's Hospital
    • San Francisco, California, United States, 94143
      • UCSF
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Rare Disease Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill Pediatrics
    • Hillsborough, North Carolina, United States, 27278
      • Rare Disease Research
  • Texas
    • Austin, Texas, United States, 78723
      • The University of Texas
    • Dallas, Texas, United States, 75243
      • Carum Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Signed informed consent from parent(s) or legal guardian(s)
• Confirmed diagnosis of AS with genetic confirmation of full maternal ubiquitin-protein ligase E3A (UBE3A) gene deletion causing AS in the region of 15q11.2 q13
• Able to ambulate independently, or with assistance at the Screening Visit (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 1.5x the normal limits at the Screening Visit
• Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, and all study procedures, including LP procedure, MRI, and tolerating anesthesia without intubation
• From the time of informed consent through to at least 6 months after the final dose of GTX-102, females of childbearing potential who are sexually active must use highly effective contraception or abstinence. Males are able to participate if they agree to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the study and for at least 3 months after the final dose of GTX-102

Key Exclusion Criteria:

• Any change in medications or diet/supplements intended to treat symptoms of AS (eg, sleeping aids, antiseizure medications, supplements, dietary change including ketogenic or low-glycemic index diet, other) within the month prior to the Screening Visit (excluding weight-based adjustments)
• Any condition that creates an increased risk of unsuccessful LP
• Current or expected concomitant use of drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors)
• Known hypersensitivity to GTX-102 or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
• Presence or history of any condition, lab abnormality, or infection, that, in the judgement of the Investigator, would interfere with participation, pose undue safety risk, or would confound interpretation of results
• Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study
• Use of any investigational product or investigational medical device within 6 months or 5 half-lives prior to the Screening Visit or any prior use of gene therapy or ASO regardless of duration since last administration
• Concurrent participation in any interventional study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GTX-102; Participants will receive GTX-102 via lumbar puncture (LP) during both the double-blind and open-label period	Drug: GTX-102; antisense oligonucleotide; Other Names: apazunersen
Sham Comparator: Sham-LP then GTX-102; Participants will receive sham procedure during the double-blind period and then will receive GTX-102 via LP during the open-label period	Drug: GTX-102; antisense oligonucleotide; Other Names: apazunersen; Procedure: Sham-LP; Small needle prick on the lower back at the location where the LP injection is normally made

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Bayley-4 Cognitive Raw Score Without Caregiver Input at Day 338	Baseline, Day 338

Secondary Outcome Measures

Outcome Measure	Time Frame
Net Response in Multidomain Responder Index (MDRI)	Day 338
Change from Baseline in ABC-C Hyperactivity/Noncompliance Subscale Score at Day 338	Baseline, Day 338
Change from Baseline in Bayley-4 Receptive Communication Raw Score at Day 338	Baseline, Day 338
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), Severity of AEs and Relationship to Investigational Drug, Procedure, and Premedication	2 Years
Change from Baseline in Angelman Severity Assessment (ASA) Sleep Rating Raw Score at Day 338	Baseline, Day 338
Change from Baseline in Vineland Adaptive Behavior Scales-3 (Vineland-3) Receptive Communication Raw Score at Day 338	Baseline, Day 338
Change from Baseline in Vineland-3 Expressive Communication Raw Score at Day 338	Baseline, Day 338
Change from Baseline in Bayley-4 Gross Motor Raw Score at Day 338	Baseline, Day 338
Change from Baseline in ASA Gross Motor Rating at Day 338	Baseline, Day 338

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Ultragenyx Patient Advocacy Website
• Ultragenyx Angelman Syndrome (AS) Research Study Opportunity
• Ultragenyx Transparency Commitment

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Angelman Syndrome
• 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-CL301; 2024-512600-19-00 (Ctis)

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