Chimeric locked nucleic acid and ribonucleic-deoxyribonucleic antisense oligonucleotide specific for the human UBE3A-antisense transcript (active substance listed as a nucleic acid ASO; productSubstances/substanceOrigin: Nucleic Acid) for Angelman syndrome

Inclusion criteria

• {"criterion_text":"- Signed informed consent from parent(s) or legal guardian(s)\n- Males and females aged 4 to < 18 years of age, inclusive, at time of informed consent\n- 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\n- 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)\n- Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time < 1.5x the upper limit of normal (CCI) at the Screening Visit\n- 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\n- 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

• {"criterion_text":"- 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)\n- Concurrent participation in any interventional study\n- Any condition that creates an increased risk of unsuccessful LP\n- Current or expected concomitant use of drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors)\n- Known hypersensitivity to GTX-102 or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects\n- 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\n- Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study\n- 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"}

Primary endpoints

• {"endpoint_text":"- Change from Baseline in Bayley-4 Cognitive Raw Score Without Caregiver Input at Day 338","definition_or_measurement_approach":"Change from baseline measured using the Bayley-4 cognitive raw score without caregiver input at Day 338."}

Secondary endpoints

• {"endpoint_text":"- Net Response in MDRI at Day 338","definition_or_measurement_approach":"Net response in MDRI assessed at Day 338."}
• {"endpoint_text":"- Change from Baseline in ABC-C Hyperactivity/Noncompliance Subscale Score at Day 338","definition_or_measurement_approach":"Change from baseline in the ABC-C Hyperactivity/Noncompliance subscale score measured at Day 338."}
• {"endpoint_text":"- Change from Baseline at Day 338 in Bayley-4 Receptive Communication raw score","definition_or_measurement_approach":"Change from baseline in Bayley-4 receptive communication raw score measured at Day 338."}
• {"endpoint_text":"- Change from Baseline in ASA Sleep Rating Raw Score at Day 338","definition_or_measurement_approach":"Change from baseline in ASA sleep rating raw score measured at Day 338."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Count and characterization of participants with treatment-emergent AEs and SAEs, including severity and relationship to investigational drug, procedure, and premedication, assessed throughout the study."}
• {"endpoint_text":"- Changes from Baseline in Vineland Adaptive Behavior Scales-3 (Vineland-3) Receptive Communication raw score at Day 338","definition_or_measurement_approach":"Change from baseline in Vineland-3 receptive communication raw score measured at Day 338."}
• {"endpoint_text":"- Changes from Baseline in Vineland-3 Expressive Communication raw score at Day 338","definition_or_measurement_approach":"Change from baseline in Vineland-3 expressive communication raw score measured at Day 338."}
• {"endpoint_text":"- Changes from Baseline in Bayley-4 Gross Motor raw score at Day 338","definition_or_measurement_approach":"Change from baseline in Bayley-4 gross motor raw score measured at Day 338."}
• {"endpoint_text":"- Changes from Baseline in ASA Gross Motor rating at day 338","definition_or_measurement_approach":"Change from baseline in ASA gross motor rating measured at Day 338."}

Methods

• Caregiver Pre-Consent Brochure (K2_ Caregiver Pre-Consent Brochure) — caregiver-facing pre-consent informational brochure available in multiple language versions (DE, ENG, ESP, POL) targeted to caregivers/parents of pediatric subjects (document identifiers present in trial documents).
• Caregiver Clinical Study Card (K2_Caregiver Clinical Study Card) — caregiver-facing study card intended for caregivers/parents (document present in trial documents).
• K1_Recruitment arrangements_Public — public recruitment arrangement materials included in trial documents (country-specific versions present).

Netherlands

Earliest CTIS Part Ii Submission Date

27-01-2025

Latest Decision Or Authorization Date

14-05-2025

Processing Time Days

107

Number Of Sites

1

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

05-12-2024

Latest Decision Or Authorization Date

18-09-2025

Processing Time Days

287

Number Of Sites

3

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

07-02-2025

Latest Decision Or Authorization Date

16-09-2025

Processing Time Days

221

Number Of Sites

4

Number Of Participants

15

Poland

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

19-09-2025

Processing Time Days

241

Number Of Sites

2

Number Of Participants

6

Primary sponsor

Full Name

Ultragenyx Pharmaceutical Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials d.o.o.

Responsibilities

Sponsor duties entries: codes 1,12,15 (Medical monitoring),5,6

Name

Icon Clinical Research Limited

Responsibilities

Sponsor duties entry: code 4

Name

Almac Clinical Services LLC

Responsibilities

IP/Placebo/Diluent Management (Depot/Clinical Supplies)

Name

Charles River Laboratories Montreal ULC

Responsibilities

Sponsor duties entry: code 4

Third parties

• {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Travel vendor for travel and site payment reimbursement/payments","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Lumanity Patient Centered Outcomes LLC","duties_or_roles":"Perform Caregiver Interviews","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Prometrika LLC","duties_or_roles":"Data Monitoring Committee (DMC)","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Cogstate Limited","duties_or_roles":"Vineland-3 Rater Training","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Code:3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"Code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"Codes:1,12,15 (Medical monitoring),5,6","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"ECG machine vendor","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"IP/Placebo/Diluent Management (Depot/Clinical Supplies)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"Long-term sample storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"Code:8","organisation_type":"Pharmaceutical company"}