Clinical trial NCT06617429: Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With AS
Official title: A Phase 3, Randomized, Double-blind, Sham-controlled Study Investigating the Efficacy and Safety of GTX-102 in Pediatric Subjects With Angelman Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Angelman Syndrome
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2024-09-27
Enrollment: 120
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in Bayley-4 Cognitive Raw Score Without Caregiver Input at Day 338
timeFrame: Baseline, Day 338
Secondary outcomes:
measure: Net Response in Multidomain Responder Index (MDRI)
timeFrame: Day 338
measure: Change from Baseline in ABC-C Hyperactivity/Noncompliance Subscale Score at Day 338
timeFrame: Baseline, Day 338
measure: Change from Baseline in Bayley-4 Receptive Communication Raw Score at Day 338
timeFrame: Baseline, Day 338
measure: Change from Baseline in Angelman Severity Assessment (ASA) Sleep Rating Raw Score at Day 338
timeFrame: Baseline, Day 338
measure: Change from Baseline in Vineland Adaptive Behavior Scales-3 (Vineland-3) Receptive Communication Raw Score at Day 338
timeFrame: Baseline, Day 338
measure: Change from Baseline in Vineland-3 Expressive Communication Raw Score at Day 338
timeFrame: Baseline, Day 338
measure: Change from Baseline in Bayley-4 Gross Motor Raw Score at Day 338
timeFrame: Baseline, Day 338
measure: Change from Baseline in ASA Gross Motor Rating at Day 338
timeFrame: Baseline, Day 338
measure: 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
timeFrame: 2 Years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: San Diego
country: United States
facility: UCSD, Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill Pediatrics
state: North Carolina
city: Hillsborough
country: United States
facility: Rare Disease Research
state: North Carolina
city: Austin
country: United States
facility: The University of Texas
state: Texas
city: Dallas
country: United States
facility: Carum Research Inc
state: Texas
city: South Brisbane
country: Australia
facility: Clinical Trial Site
city: Sydney
country: Australia
facility: Clinical Trial Site
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Leipzig
country: Germany
facility: University of Leipzig
city: Munich
country: Germany
facility: Haunersche Kinderklinik
city: Nagoya
country: Japan
facility: Nagoya City University Graduate School of Medical Sciences
state: Aichi
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Rotterdam
country: Netherlands
facility: Clinical Trial Site
city: Gdańsk
country: Poland
facility: Medical University of Gdańsk
city: Łódź
country: Poland
facility: Polish Mothers Memorial Institute
city: Barcelona
country: Spain
facility: Hospital Universitario Parc Tauli
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Seville
country: Spain
facility: Clinical Trial Site
Study officials:
affiliation: Ultragenyx Pharmaceuticals Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: