Angelman Syndrome
Conditions
Keywords
Angelman Syndrome
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).
Interventions
PROCEDURESham-LP
Small needle prick on the lower back at the location where the LP injection is normally made
DRUGGTX-102
antisense oligonucleotide
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in Bayley-4 Cognitive Raw Score Without Caregiver Input at Day 338 | Baseline, Day 338 |
Secondary
| 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 |
| 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 |
| 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 |
Countries
Canada, Germany, Japan, Poland, Spain, United States
Contacts
STUDY_DIRECTORMedical Director
Ultragenyx Pharmaceuticals Inc.
Outcome results
None listed