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

NCT06617429 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: GTX-102-CL3012024-512600-19-00
• Study Type: interventional
• Target: 129
• Locations: 6 countries
• Sites: 28

Brief Summary

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).

Conditions

Angelman Syndrome

Keywords

Angelman Syndrome

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Bayley-4 Cognitive Raw Score Without Caregiver Input at Day 338

  Baseline, Day 338

Secondary Outcomes (9)

• 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

• 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

Study Arms (2)

GTX-102

EXPERIMENTAL

Participants will receive GTX-102 via lumbar puncture (LP) during both the double-blind and open-label period

Drug: GTX-102

Sham-LP then GTX-102

SHAM COMPARATOR

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; Procedure: Sham-LP

Interventions

Sham-LP PROCEDURE

Small needle prick on the lower back at the location where the LP injection is normally made

Sham-LP then GTX-102

GTX-102 DRUG

antisense oligonucleotide

Also known as: apazunersen

GTX-102; Sham-LP then GTX-102

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (28)

Cedars Sinai

Los Angeles, California, 90048, United States

Location

UCSD, Rady Children's Hospital

San Diego, California, 92123, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Rare Disease Research

Atlanta, Georgia, 30329, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Mercy

Kansas City, Missouri, 64108, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UNC Chapel Hill Pediatrics

Chapel Hill, North Carolina, 27599, United States

Location

Rare Disease Research

Hillsborough, North Carolina, 27278, United States

Location

The University of Texas

Austin, Texas, 78723, United States

Location

Carum Research Inc

Dallas, Texas, 75243, United States

Location

McGill University Health Centre

Montreal, Quebec, H4A3J1, Canada

Location

British Columbia Children's Hospital

Vancouver, V6H 3V4, Canada

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20251, Germany

Location

University of Leipzig

Leipzig, 04155, Germany

Location

Haunersche Kinderklinik

Munich, 80336, Germany

Location

Nagoya City University Graduate School of Medical Sciences

Nagoya, Aichi-ken, 467-0001, Japan

Location

Osaka City General Hospital

Osaka, 543-0021, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Medical University of Gdańsk

Gdansk, 80211, Poland

Location

Polish Mothers Memorial Institute

Lodz, 93-338, Poland

Location

Hospital Universitario Parc Tauli

Barcelona, 08208, Spain

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28222, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Related Links

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

MeSH Terms

Conditions

Angelman Syndrome

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Study Officials

• Medical Director

  Ultragenyx Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: September 27, 2024
• Study Start: December 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2); CA (2); JP (3); ES (4); DE (3); US (14)