Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
98
Countries
3
Sites
6
Angelman Syndrome
Evaluate the long-term safety profile of GTX-102 in subjects with AS
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
- 3 Sep 2024 → ongoing
- Decision date (initial)
- 2024-07-19
- 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, Safety
Evaluate the long-term safety profile of GTX-102 in subjects with AS
Secondary objectives 1
- To evaluate the long-term efficacy of GTX-102 in cognitive function, communication, and motor skills and function.
Conditions and MedDRA coding
Angelman Syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10049004 | Angelman's syndrome | 100000004850 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening period Subjects will enter this study after participating in a GTX-102 clinical trial. All subjects will undergo assessments at Screening/Month 0 and throughout the study as indicated in Table 3 of the Protocol.
|
Not Applicable | None | ||
| 2 | Treatment period Subjects will receive treatment with GTX-102 via intrathecal (IT) lumbar puncture (LP). Subjects may remain in the study until GTX-102 is approved and/or becomes available in their geographical region.
|
Not Applicable | None | ||
| 3 | Safety follow-up A safety follow-up telephone call will occur 30 days after the EOS/ET Visit for subjects who have a new or ongoing TEAE at their EOS/ET Visit or for subjects whose EOS/ET Visit coincided with a Dosing Visit, in which they received GTX-102.
|
Not Applicable | None |
Regulatory references
- Plan to share IPD
- No
- IPD plan description
- N/A
| EU CT number | Title | Sponsor |
|---|---|---|
| 2021-001793-36 | A Phase 1/2 Open-label, Multiple-dose, Dose-escalating Clinical Trial of the Safety and Tolerability of GTX-102 in Pediatric Patients With Angelman Syndrome (AS) , Ensayo clínico de fase 1/2, abierto, de dosis múltiples y de aumento gradual de la dosis para evaluar la seguridad y la tolerabilidad de GTX-102 en pacientes pediátricos con síndrome de Angelman (SA) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Signed informed consent from parent(s) or legal guardian(s).
- Completed a final study visit in a prior clinical trial with GTX-102. If the subject has an ongoing adverse event (AE), Medical Monitor approval is required to rollover. The Screening visit must occur within 6 months of the last visit in the prior GTX-102 study.
- From the time of informed consent through the end of the study and for 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 4
- Discontinued from prior GTX-102 trial due to treatment-emergent adverse event assessed as related to GTX-102 and where the risk of study participation outweighs the benefits as deemed by the clinical judgment of the Investigator.
- History or evidence of any other medical, neurological, or psychological condition that would expose the subject to an undue risk of a significant AE or interfere with study assessments during the course of the trial as determined by the clinical judgment of the Investigator.
- Known hypersensitivity to GTX-102 or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
- Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Treatment-emergent AEs and SAEs, frequency, severity, and relationship to investigational product throughout the study
Secondary endpoints 1
- Change from LTE Month 0 and pretreatment (when available) throughout the study in: • Bayley-4 Cognitive raw score • Bayley-4 Receptive Communication raw score • Bayley-4 Expressive Communication raw score • Bayley-4 Gross Motor raw score • Bayley-4 Fine Motor raw score
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD11237423 · Product
- Active substance
- Apazunersen
- Substance synonyms
- ASO-4.4.PS.L, 2'-O, 4'-methyleneadenylyl-(3'-thio-5')-2'-O, 4'-methyleneguanylyl-(3'-thio5')-2'-O, 4'-methyleneadenylyl-(3'-thio-5')-2'-deoxyadenylyl-(3'-thio-5')-thymidyl-(3'-thio-5')-2'-deoxyguanylyl-(3'-thio-5')-2'-deoxyguanylyl-(3'-thio5')-2'-deoxycytidylyl-(3'-thio-5')-2'-deoxyadenylyl-(3'-thio-5')-2'-deoxycytidylyl-(3'-thio-5')-2'-deoxyadenylyl-(3'-thio-5')-thymidyl-(3'-thio-5')- 2'-deoxycytidylyl-(3'-thio-5')-thymidyl-(3'-thio-5')-2'-O, 4'-methylene-5-methylcytidylyl-(3'-thio-5')-2'-O, 4'-methylene-5-methyluridylyl-(3'-thio-5')-2'-O, 4'-methylene-5-methyluridylyl-(3'-thio-5')-2'-O, 4'-methyleneguanylyl, GTX-102, 2'-O, 4'-C-Methylene-P-thio-adenylyl-(3'->5')-2'-O, 4'-C-methylene-P-thioguanylyl-(3'->5')-2'-O, 4'-C-methylene-P-thio-adenylyl-(3'->5')-2'-deoxy-P-thioadenylyl-(3'->5')-2'-deoxy-P-thio-thymidylyl-(3'->5')-2'-deoxy-P-thio-guanylyl-(3'->5')-2'-deoxy-P-thio-guanylyl-(3'->5')-2'-deoxy-P-thio-cytidylyl-(3'->5')-2'-deoxy-P-thio-adenylyl-(3'->5')-2'-deoxy-P-thio-cytidylyl-(3'->5')-2'-deoxy-P-thio-adenylyl-(3'->5')-2'-deoxy-P-thio-thymidylyl-(3'->5')-2'-deoxy-P-thio-cytidylyl-(3'->5')-2'-deoxy-P-thio-thymidylyl-(3'->5')-2'-O, 4'-C-methylene-5-methyl-P-thio-cytidylyl-(3'->5')-2'-O, 4'-C-methylene-5-methyl-P-thio-uridylyl-(3'->5')-2'-O, 4'-C-methylene-5-methyl-P-thio-uridylyl-(3'->5')-2'-O, 4'-C-methyleneguanosine, Chimeric locked nucleic acid and ribonucleic-deoxyribonucleic antisense oligonucleotide specific for the human UBE3A-antisense transcript
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATHECAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ULTRAGENYX PHARMACEUTICAL INC.
- Paediatric formulation
- Yes
- Orphan designation
- Yes
- Orphan designation number
- EU/3/23/2869
Auxiliary 2
ELLIOTTS B SOLUTION (buffered intrathecal electrolyte/dextrose injection)
PRD11193195 · Product
- Active substance
- Calcium Chloride
- Pharmaceutical form
- SOLUTION FOR SOLUTION FOR INJECTION
- Route of administration
- INTRATHECAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ULTRAGENYX PHARMACEUTICAL INC.
- Paediatric formulation
- No
- Orphan designation
- No
GTX/UX Diluent and Flush Solution
PRD11403616 · Product
- Active substance
- Sodium Dihydrogen Phosphate Dihydrate
- Other product name
- DFS
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATHECAL USE
- Max daily dose
- 00 mg/ml milligram(s)/millilitre
- Max total dose
- 00 mg/ml milligram(s)/millilitre
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ULTRAGENYX PHARMACEUTICAL INC.
- Paediatric formulation
- No
- Orphan designation
- No
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 12
| Organisation | City, country | Duties |
|---|---|---|
| Primevigilance Limited ORG-100027742
|
Guildford, United Kingdom | Code 8 |
| Suvoda LLC ORG-100043523
|
Conshohocken, United States | Interactive response technologies (IRT) |
| Almac Clinical Services Limited ORG-100017464
|
Craigavon, United Kingdom (Northern Ireland) | Code 14 |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | Laboratory analysis |
| Yprime LLC ORG-100042888
|
Malvern, United States | Other, E-data capture |
| Worldwide Clinical Trials d.o.o. ORG-100030991
|
Zagreb, Croatia | On site monitoring, Code 12, Code 5, Data management |
| Gray Consulting Inc. ORG-100044159
|
Philadelphia, United States | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Charles River Laboratories Montreal ULC ORG-100041009
|
Sherbrooke, Canada | Laboratory analysis |
| Clario eResearch Technology GmbH ORL-000010431
|
Estenfeld, Germany | Other |
| Veeva Systems Inc. ORG-100006053
|
Pleasanton, United States | Other |
| EPL Pathology Archives LLC ORG-100042096
|
Sterling, United States | Other |
Locations
3 EU/EEA countries · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 11 | 2 |
| Germany | Ongoing, recruiting | 10 | 2 |
| Spain | Ongoing, recruiting | 17 | 2 |
| Rest of world
Canada, Israel, United States, United Kingdom, Australia
|
— | 60 | — |
Investigational sites
Centre Hospitalier Regional De Marseille
Hôpital d’enfants de la Timone, 264 Rue Saint Pierre, 13005, Marseille
Hopital Necker Enfants Malades
Neurologie Pédiatrique, 149 Rue De Sevres, 75015, Paris
University Medical Center Hamburg-Eppendorf
Pediatric Neurology, Martinistrasse 52, Eppendorf, Hamburg
Universitaet Leipzig
Pediatric Neurology, Liebigstrasse 20a, Zentrum-Suedost, Leipzig
Parc Tauli Hospital Universitari
Pediatric, Parc Del Tauli 1 Edifici Santa Fe Ala Izquierda Planta 2ª, 08208, Sabadell
Hospital Universitario Puerta De Hierro De Majadahonda
Pediatric, Calle De Joaquin Rodrigo 2, 28222, Majadahonda
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-09-03 | 2024-09-12 | |||
| Germany | 2024-09-17 | 2024-09-24 | |||
| Spain | 2024-09-27 | 2024-10-15 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 39 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Pharmacy Manual_2024-510917-14_Redaction Placeholder | NA |
| Protocol (for publication) | D1_Protocol_2024-510917-14_Redacted | 1 |
| Protocol (for publication) | D4_Patient facing documents Administration Manual_DEU_redaction placeholder | NA |
| Protocol (for publication) | D4_Patient facing documents Administration Manual_ENG_redaction placeholder | NA |
| Protocol (for publication) | D4_Patient facing documents Administration Manual_FRA_redaction placeholder | NA |
| Protocol (for publication) | D4_Patient facing documents Administration Manual_SPA_redaction placeholder | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4 Stimulus book content DEU_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4 Stimulus book content ENG_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4 Stimulus book content ESP_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4 Stimulus book content FRA_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Motor Response Booklet DEU_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Motor Response Booklet ENG_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Motor Response Booklet ESP_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Motor Response Booklet FRA_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Record form DEU_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Record form ENG_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Record form ESP_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Record form FRA_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book cover DEU_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book cover ENG_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book cover ESP_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book cover FRA_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book tabs DEU_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book tabs ENG_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book tabs ESP_redaction placeholder_Public | NA |
| Protocol (for publication) | D4_Patient facing documents_Bayley-4_Stimulus book tabs FRA_redaction placeholder_Public | NA |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement_FRA-Fre | 1.1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.1 |
| Recruitment arrangements (for publication) | K1_Recruitment_arrangements | 1.1 |
| Subject information and informed consent form (for publication) | L1_ ICF Parent Guardian_ESP_Redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_ParentGuardian_ICF_DE_redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Clincierge_Data Protection Notice_DPO change_FRA-Fre | N/A |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Clincierge_Data Protection Notice_FRA-Fre | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_FRA-Fre_Redacted | 2.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Placeholder | NA |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_DEU_2024-510917-14_Redacted | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG_2024-510917-14_Redacted | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_FRA_2024-510917-14_Redacted | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_SPA_2024-510917-14_Redacted | 1 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-15 | Spain | Acceptable 2024-07-18
|
2024-07-18 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-14 | Spain | Acceptable | 2024-09-20 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-08-14 | Acceptable | 2024-09-16 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-08-14 | Acceptable | 2024-10-26 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-11-26 | Spain | Acceptable 2025-03-17
|
2025-03-17 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-09-24 | Spain | Acceptable 2025-11-11
|
2025-11-12 |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-02-16 | Acceptable 2025-11-11
|
2026-02-16 |