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Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With AS

Phase 3
Recruiting
Conditions
Angelman Syndrome
Interventions
Procedure: Sham-LP
Registration Number
NCT06617429
Lead Sponsor
Ultragenyx Pharmaceutical Inc
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GTX-102GTX-102Participants will receive GTX-102 via lumbar puncture (LP) during both the double-blind and open-label period
Sham-LP then GTX-102GTX-102Participants will receive sham procedure during the double-blind period and then will receive GTX-102 via LP during the open-label period
Sham-LP then GTX-102Sham-LPParticipants will receive sham procedure during the double-blind period and then will receive GTX-102 via LP during the open-label period
Primary Outcome Measures
NameTimeMethod
Change from Baseline in Bayley-4 Cognitive Raw Score Without Caregiver Input at Day 338Baseline, Day 338
Secondary Outcome Measures
NameTimeMethod
Net Response in Multidomain Responder Index (MDRI)Day 338
Change from Baseline in ABC-C Hyperactivity/Noncompliance Subscale Score at Day 338Baseline, Day 338
Change from Baseline in Bayley-4 Receptive Communication Raw Score at Day 338Baseline, Day 338
Change from Baseline in Angelman Severity Assessment (ASA) Sleep Rating Raw Score at Day 338Baseline, Day 338
Change from Baseline in Vineland Adaptive Behavior Scales-3 (Vineland-3) Receptive Communication Raw Score at Day 338Baseline, Day 338
Change from Baseline in Vineland-3 Expressive Communication Raw Score at Day 338Baseline, Day 338
Change from Baseline in Bayley-4 Gross Motor Raw Score at Day 338Baseline, Day 338
Change from Baseline in ASA Gross Motor Rating at Day 338Baseline, 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 Premedication2 Years

Trial Locations

Locations (23)

Clinical Trial Site

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Seville, Spain

University of Leipzig

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Leipzig, Germany

Nagoya City University Graduate School of Medical Sciences

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Nagoya, Aichi, Japan

Cedars Sinai

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Los Angeles, California, United States

UCSD, Rady Children's Hospital

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San Diego, California, United States

UCSF

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San Francisco, California, United States

Nicklaus Children's Hospital

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Miami, Florida, United States

Rare Disease Research

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Hillsborough, North Carolina, United States

Rush University

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Chicago, Illinois, United States

Boston Children's Hospital

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Boston, Massachusetts, United States

Children's Mercy

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Kansas City, Missouri, United States

Columbia University Medical Center

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New York, New York, United States

UNC Chapel Hill Pediatrics

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Chapel Hill, North Carolina, United States

The University of Texas

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Austin, Texas, United States

Carum Research Inc

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Dallas, Texas, United States

British Columbia Children's Hospital

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Vancouver, Canada

Universitaetsklinikum Hamburg-Eppendorf

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Hamburg, Germany

Haunersche Kinderklinik

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Munich, Germany

Osaka City General Hospital

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Osaka, Japan

Hokkaido University Hospital

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Sapporo, Japan

Medical University of GdaΕ„sk

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GdaΕ„sk, Poland

Polish Mothers Memorial Institute

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Łódź, Poland

Hospital Universitario Parc Tauli

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Barcelona, Spain

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