Apazunersen for Angelman syndrome

Inclusion criteria

• {"criterion_text":"- Signed informed consent from parent(s) or legal guardian(s)\n- 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.\n- Weight ≥ 8 kg at Screening Visit.\n- 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.\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- 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 or required premedication 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 study 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 an ASO regardless of length of time since last use.\n- Concurrent participation in any interventional study."}

Primary endpoints

• {"endpoint_text":"- All Subprotocols - Primary Safety Endpoint: TEAEs and SAEs, frequency, severity, and relationship to investigational product, procedure, and premedication throughout the study.","definition_or_measurement_approach":"Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be recorded throughout the study; endpoints describe frequency, severity, and relationship to investigational product, procedure, and premedication. Specific safety assessment schedules are not provided in the JSON."}
• {"endpoint_text":"- Subprotocol GTX-102-CL210A - Primary Efficacy Endpoint: Bayley-4 Cognitive raw score without caregiver input, change from Baseline at Day 338.","definition_or_measurement_approach":"Change from baseline in Bayley-4 Cognitive raw score (without caregiver input) measured at Day 338 compared to baseline."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"MDRI Net response at Day 338 combining listed domain assessments (Bayley-4 Cognitive and Receptive Communication, ABC-C Hyperactivity/Noncompliance, ASA Sleep rating, ASA Gross Motor rating). MDRI methodology referenced but not detailed in JSON."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"MDRI Net response at Day 338 combining Vineland-3 expressive and receptive communication raw scores, ABC-C irritability subscale, and ASA Gross Motor rating. MDRI methodology not further defined in JSON."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"MDRI Net response at treatment Day 338 combining domain assessments as listed (Bayley-4, ABC-C, ASA ratings). MDRI methodology not specified in JSON."}

Secondary endpoints

• {"endpoint_text":"- Subprotocol GTX-102-CL210A - Change from Baseline at Day 338 in: Bayley-4 Receptive Communication raw score, Bayley-4 Gross Motor raw score","definition_or_measurement_approach":"Change from baseline to Day 338 in Bayley-4 Receptive Communication raw score and Bayley-4 Gross Motor raw score."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change from baseline to Day 338 in the listed cognitive, communication, behavior, sleep, and motor assessments."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change from baseline to Day 338 in Vineland-3 receptive and expressive communication raw scores, ABC-C irritability subscale, and ASA Gross Motor rating."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change from baseline (or pretreatment) to treatment Day 338 in the listed scales across cognitive, communication, behavior, sleep, and motor function measures."}

Methods

• Recruitment materials and arrangements documented (K1_Recruitment_arrangements_Public documents listed).
• Sponsor contact for trial recruitment: Ultragenyx trial information group (Trialrecruitment@ultragenyx.com) for enquiries.
• Participant travel arrangements and expense reimbursement managed by Gray Consulting Inc. / Clincierge (documented services).
• Telehealth visits supported (Clinical Ink Inc. listed with role 'Telehealth visits').
• Site-based recruitment through participating hospital/clinic sites in Portugal, France and Italy (listed trial sites).
• Plain language summaries and participant letters (documents such as Plain Language Summary Patient Letter and GP Letter are included among study documents).

Portugal

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

16-04-2026

Processing Time Days

181

Number Of Sites

2

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

27-10-2025

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

176

Number Of Sites

3

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

10-11-2025

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

168

Number Of Sites

3

Number Of Participants

9

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.

Name

Icon Clinical Research Limited

Name

Almac Clinical Services LLC

Responsibilities

IMP/Diluent management, Depot/Clinical Supplies

Name

Primevigilance Limited

Name

Prometrika LLC

Responsibilities

Data Monitoring Committee (DMC) management

Name

Gray Consulting Inc.

Responsibilities

Participant travel arrangements and expenses reimbursement, site reimbursement payments

Third parties

• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Participant travel arrangements and expenses reimbursement, site reimbursement payments","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Prometrika LLC","duties_or_roles":"Data Monitoring Committee (DMC) management","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Mapi Research Trust","duties_or_roles":"Scale (COA) licensing and management","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Cogstate Limited","duties_or_roles":"Scale (including Vineland-3) rater training; Performing Assessments","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"Telehealth visits","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Corticare Inc.","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"eTMF","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"IMP/Diluent management, Depot/Clinical Supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"Laboratory sample storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Clario Medical Imaging Inc.","duties_or_roles":"ECG supply and central reading","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Prometrika LLC","duties_or_roles":"Data Monitoring Committee (DMC) management","organisation_type":"Pharmaceutical company"}