A Safety and Efficacy Study of GTX-102 in Subjects with Deletion- or Nondeletion-type Angelman Syndrome (Aurora)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ultragenyx Pharmaceutical Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Feb 2026 → ongoing

Decision date (initial)

2026-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ultragenyx Pharmaceutical Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

Primary Safety Objective: evaluate the safety of GTX-102.
Primary Efficacy Objective: evaluate the efficacy of GTX-102.

Secondary objectives 1

1. Secondary Objective: evaluate the effect of GTX-102 on key AS-defining domains.

Conditions and MedDRA coding

Angelman Syndrome

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003595-PIP01-24

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent from parent(s) or legal guardian(s)
2. Males and females of the following ages and genotypes at time of informed consent: a. Subprotocol A: ≥ 1 to < 4 years of age with a genetically confirmed diagnosis of deletion-type Angelman Syndrome b. Subprotocol B: ≥ 4 to < 18 years of age with a genetically confirmed diagnosis of UPD/ICD Angelman Syndrome c. Subprotocol C: ≥ 18 to < 65 years of age with a genetically confirmed diagnosis of Angelman Syndrome, any genotype d. Subprotocol D: ≥ 4 to < 18 years of age with a genetically confirmed diagnosis of mutation-type Angelman Syndrome.
3. Weight ≥ 8 kg at Screening Visit.
4. Prothrombin time / international normalized ratio, and partial thromboplastin time < 1.5x the upper limit of normal and platelets > 75,000 cells/mm3 at the Screening Visit.
5. 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.
6. 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.

Exclusion criteria 8

1. 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).
2. Any condition that creates an increased risk of unsuccessful LP.
3. Current or expected concomitant use of drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors).
4. Known hypersensitivity to GTX-102 or its excipients or required premedication that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
5. Presence or history of any condition, lab abnormality, or infection that, in the judgement of the Investigator, would interfere with study participation, pose undue safety risk, or would confound interpretation of results.
6. Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study.
7. 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 an ASO regardless of length of time since last use.
8. Concurrent participation in any interventional study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. All Subprotocols - Primary Safety Endpoint: TEAEs and SAEs, frequency, severity, and relationship to investigational product, procedure, and premedication throughout the study.
2. Subprotocol GTX-102-CL210A - Primary Efficacy Endpoint: Bayley-4 Cognitive raw score without caregiver input, change from Baseline at Day 338.
3. Subprotocol GTX-102-CL210B - Primary Efficacy Endpoint: MDRI Net response at Day 338, with the following domains - assessments: Cognition - Bayley-4 Cognitive raw score, Communication - Bayley-4 Receptive Communication raw score, Behavior - ABC-C Hyperactivity/Noncompliance, Sleep - ASA Sleep rating, Motor Function - ASA Gross Motor rating.
4. Subprotocol GTX-102-CL210C - Primary Efficacy Endpoint: MDRI Net response at Day 338, with the following domains - assessments: Expressive Communication - Vineland-3 Expressive Communication raw score, Receptive Communication – Vineland-3 Receptive Communication raw score, Behavior - ABC-C Irritability subscale score, Motor Function - ASA Gross Motor rating.
5. Subprotocol GTX-102-CL210D - Primary Efficacy Endpoint: MDRI Net response at TxD 338, with the following domains - assessments: Cognition - Bayley-4 Cognitive raw score, Communication - Bayley-4 Receptive Communication raw score, Behavior - ABC-C Hyperactivity/Noncompliance, Sleep - ASA Sleep rating, Motor Function - ASA Gross Motor rating.

Secondary endpoints 4

1. Subprotocol GTX-102-CL210A - Change from Baseline at Day 338 in: Bayley-4 Receptive Communication raw score, Bayley-4 Gross Motor raw score
2. Subprotocol GTX-102-CL210B - Change from Baseline at Day 338 in: Bayley-4 Cognitive raw score, Bayley-4 Receptive Communication raw score, Vineland-3 Receptive Communication raw score, Vineland-3 Expressive Communication raw score, ABC-C Hyperactivity/Noncompliance subscale score, ASA Sleep rating, ASA Gross Motor rating, Bayley-4 Gross Motor raw score.
3. Subprotocol GTX-102-CL210C - Change from Baseline at Day 338 in: Vineland-3 Receptive Communication raw score, Vineland-3 Expressive Communication raw score, ABC-C Irritability subscale score, ASA Gross Motor rating.
4. Subprotocol GTX-102-CL210D - Change from Baseline (or pretreatment) at TxD 338: Bayley-4 Cognitive raw score, Bayley-4 Receptive Communication raw score, Vineland-3 Receptive Communication raw score, Vineland-3 Expressive Communication raw score, ABC-C Hyperactivity/Noncompliance subscale score, ASA Sleep rating, ASA Gross Motor rating, Bayley-4 Gross Motor raw score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ultragenyx Pharmaceutical Inc.

Sponsor organisation

Ultragenyx Pharmaceutical Inc.

Address

60 Leveroni Court Suite 200

City

Novato

Postcode

94949-5746

Country

United States

Scientific contact point

Organisation

Ultragenyx Pharmaceutical Inc.

Contact name

Medical Information

Public contact point

Organisation

Ultragenyx Pharmaceutical Inc.

Contact name

Ultragenyx trial information group

Third parties 17

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications