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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ultragenyx Pharmaceutical Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

14 Apr 2025 → ongoing

Decision date (initial)

2025-02-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ultragenyx Pharmaceutical Inc.

External identifiers

EU CT number

2024-512600-19-00

ClinicalTrials.gov

NCT06617429

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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).

Secondary objectives 1

1. The secondary objectives are to evaluate the effect of GTX-102 in subjects with deletion-type AS in communication, behavior, sleep, and motor function; as well as evaluate the safety of GTX-102.

Conditions and MedDRA coding

Angelman Syndrome

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Federal Institute For Drugs And Medical Devices, Medicines Evaluation Board, Swedish Medical Products 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 7

1. Signed informed consent from parent(s) or legal guardian(s)
2. Males and females aged 4 to < 18 years of age, inclusive, at time of informed consent
3. 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
4. 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)
5. Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time < 1.5x the upper limit of normal (CCI) at the Screening Visit
6. 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
7. 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. Concurrent participation in any interventional study
3. Any condition that creates an increased risk of unsuccessful LP
4. Current or expected concomitant use of drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors)
5. Known hypersensitivity to GTX-102 or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
6. 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
7. Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study
8. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 9

1. Net Response in MDRI at Day 338
2. Change from Baseline in ABC-C Hyperactivity/Noncompliance Subscale Score at Day 338
3. Change from Baseline at Day 338 in Bayley-4 Receptive Communication raw score
4. Change from Baseline in ASA Sleep Rating Raw Score at Day 338
5. 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
6. Changes from Baseline in Vineland Adaptive Behavior Scales-3 (Vineland-3) Receptive Communication raw score at Day 338
7. Changes from Baseline in Vineland-3 Expressive Communication raw score at Day 338
8. Changes from Baseline in Bayley-4 Gross Motor raw score at Day 338
9. Changes from Baseline in ASA Gross Motor rating at day 338

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

Medical Information

Third parties 14

Locations

4 EU/EEA countries · 10 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 25 files

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

Application history

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