Angelman SyndromePhase 1/2NCT04259281
A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome
A Phase 1/2 study testing GTX-102 in people with Angelman Syndrome, run by Ultragenyx Pharmaceutical Inc at 25 sites in 8 countries.
Trial summary
The primary objective of the study is to evaluate the safety and tolerability of multiple-ascending doses of GTX-102 administered by intrathecal (IT) injection to participants with Angelman Syndrome (AS). Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- GTX-102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 25 sitesin 8 countries
- Study dates
- 24 Feb 2020to 8 Jan 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed informed consent from parent(s) or legal guardian(s)
- Documented genetic confirmation of full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13 including class I, II or III
- Stable seizure control (defined as clinically stable with no changes in antiepileptic medications over the prior 1 month before the screening visit, other than weight associated dose adjustments)
- Able to ambulate independently, or with an assistive device (note, a child whose primary means of mobility is by wheelchair is excluded from the study)
- Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time within 1.2 x the normal limits
- Normal renal function with serum creatinine and spot urine protein ≤ 1.4 x the upper limit of normal (ULN)
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- Normal hepatic function with total bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≤ 1.4 x ULN. Exception: levels ≤ 2 × ULN are acceptable if due to anti-epileptic drugs (AEDs) or Gilbert syndrome
- Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures, including LP procedure
- Able to tolerate the anesthetic regimen, if required for LP procedure
- A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Female of non-childbearing potential (ie, pre-menarche), Female of childbearing potential who agrees to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 3 months after the final dose of GTX-102
- A male patient is eligible to participate if he agrees to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 3 months after the final dose of GTX-102
Who cannot join
- Any change in medications (excluding AEDs) or diet/supplements intended to treat symptoms of AS (eg, sleeping aids, supplements, dietary change including ketogenic or low-glycemic index diet, other) over the prior 1 month before screening
- Any bleeding or platelet disorder
- Any clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurological, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, make the patient unsuitable for participation in, and/or unable to complete the study procedures
- Any laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study result
- Known positive for hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
- Any active infection
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- Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
- Drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors)
- Any prior use of gene therapy
- Use of any investigational drugs in the past 6 months or within 5 half-lives, whichever period is greater (with the exception of prior GTX 102)
- Known hypersensitivity to any oligonucleotide, as demonstrated by an immune mediated reaction (eg, pneumonitis, hepatitis, nephritis, neuritis, or other system inflammation), or a systemic allergic reaction such as signs and symptoms of anaphylaxis, urticaria, clinically significant rash
- Patient is pregnant or lactating
- Any medical condition that would require intubation for the anesthesia procedure
Trial locations and contacts
25 sites in 8 countries.
25 sites in 8 countries
United States6 sites
Rare Disease Research
Atlanta, Georgia, 30318
Boston Children's Hospital
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
UCLA Medical Center
Los Angeles, California, 90095
Weill Cornell Medicine
New York, New York, 10065
Rady Children's Hospital
San Diego, California, 92123
Canada5 sites
MAGIC Clinic Ltd
Calgary, Alberta, T2E 7Z4
Children's Hospital of Western Ontario
London, Ontario
McGill University Health Centre
Montreal, Quebec
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
British Columbia Children's Hospital
Vancouver, British Columbia, V6H3V4
Australia3 sites
Austin Health
Heidelberg, Victoria, 3084
The Royal Children's Hospital
Parkville, Victoria, 3052
Queensland Children's Hospital
South Brisbane, QLD 4101
Spain3 sites
Hospital Sant Joan de Deu
Esplugues de Llobregat, Barcelona
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid
Hospital Universitari Parc Tauli
Sabadell, Barcelona
United Kingdom3 sites
Cambridge University Hospitals
Cambridge
Great Ormond Street Hospital for Children
London
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 7LE
France2 sites
Hopital de la Timone
Marseille
AP-HP Hopital Necker-Enfants Malades
Paris, 75015
Germany2 sites
Universitatsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitatsklinikum Leipzig
Leipzig, Saxony, 04103
About this study
Official title: 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)
The primary objective of the study is to evaluate the safety and tolerability of multiple-ascending doses of GTX-102 administered by intrathecal (IT) injection to participants with Angelman Syndrome (AS).
Read the detailed description
This is a Phase 1/2, open-label, multiple-dose, study to evaluate the safety, tolerability, and plasma and CSF concentrations of GTX-102 in pediatric participants with AS.
The study includes a Loading phase followed by a Maintenance phase. Participants may continue on GTX-102 during the Maintenance phase of the study until GTX-102 is commercially available, intolerable toxicity occurs, the parent/legal guardian withdraws consent, the participant enrolls in another experimental study, or this study is terminated.
This study was previously posted by GeneTX Biotherapeutics, LLC and was transferred to Ultragenyx in July 2022.
- Conditions
- Angelman Syndrome
- Being tested
- GTX-102
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GTX-102Drug
antisense oligonucleotide
| Study group | Role | What they receive |
|---|---|---|
| GTX-102 Cohort 1 | Experimental | 3.3 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to <17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort 2 | Experimental | 10 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to <17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort 3 | Experimental | 20 mg starting dose followed by intra-patient dose escalation up to 55 mg and then a maintenance phase (in U.S participants 4 to <17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort 4 | Experimental | 3.3 mg starting dose followed by slow intra-patient dose escalation up to 5 mg and then a maintenance phase (in Ex-U.S participants 4 to <8 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort 5 | Experimental | 5 mg starting dose followed by slow intra-patient dose escalation up to 7.5 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort 6 | Experimental | 7.5 mg starting dose followed by slow intra-patient dose escalation up to 10 mg and then a maintenance phase (in Ex-U.S participants 4 to <8 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort 7 | Experimental | 10 mg starting dose followed by slow intra-patient dose escalation up to 12 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort US | Experimental | 2 mg for 4 monthly doses followed by a quarterly maintenance regimen Receives: Drug: GTX-102 |
| GTX-102 Expanded Enrollment Cohort A | Experimental | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants 4 to <8 years of age) Receives: Drug: GTX-102 |
| GTX-102 Expanded Enrollment Cohort B | Experimental | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Expanded Enrollment Cohort C | Experimental | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants 4 to <8 years of age) Receives: Drug: GTX-102 |
| GTX-102 Expanded Enrollment Cohort D | Experimental | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants ≥ 8 to 17 years of age) Receives: Drug: GTX-102 |
| GTX-102 Cohort E | Experimental | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in participants that transition from GTX-102 US Cohort only) Receives: Drug: GTX-102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), Adverse Events of Special Interest (AESIs), AEs Leading to Discontinuation and Severity of AEs
Measured: Up to Day 337
Secondary outcomes (1)
Pharmacokinetics of GTX-102 over time
Maximum drug concentration (Cmax)
Measured: Up to Day 337
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start24 Feb 2020
- Primary completion8 Jan 2025
- Study completion8 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04259281
- Sponsor's protocol ID
- GTX-102-001
- Other IDs
- 2021-001793-36
- Status last verified
- Jan 2026
- First submitted
- 31 Jan 2020
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dindot SV, Christian S, Murphy WJ, Berent A, Panagoulias J, Schlafer A, Ballard J, Radeva K, Robinson R, Myers L, Jepp T, Shaheen H, Hillman P, Konganti K, Hillhouse A, Bredemeyer KR, Black L, Douville J; FIRE consortium; FIRE Consortium. An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the UBE3A-AS transcript. Sci Transl Med. 2023 Mar 22;15(688):eabf4077. doi: 10.1126/scitranslmed.abf4077. Epub 2023 Mar 22.
PubMed 36947593
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04259281
- Acronym / sponsor ID
- GTX-102-001
- Conditions
- Angelman Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 8 Jan 2025 (actual)
- Study completion
- 8 Jan 2025 (actual)
- First posted
- 6 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to evaluate the safety and tolerability of multiple-ascending doses of GTX-102 administered by intrathecal (IT) injection to participants with Angelman Syndrome (AS).
Detailed description
This is a Phase 1/2, open-label, multiple-dose, study to evaluate the safety, tolerability, and plasma and CSF concentrations of GTX-102 in pediatric participants with AS.
The study includes a Loading phase followed by a Maintenance phase. Participants may continue on GTX-102 during the Maintenance phase of the study until GTX-102 is commercially available, intolerable toxicity occurs, the parent/legal guardian withdraws consent, the participant enrolls in another experimental study, or this study is terminated.
This study was previously posted by GeneTX Biotherapeutics, LLC and was transferred to Ultragenyx in July 2022.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| GTX-102 Cohort 1 | Experimental | Drug: GTX-1023.3 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to <17 years of age) |
| GTX-102 Cohort 2 | Experimental | Drug: GTX-10210 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to <17 years of age) |
| GTX-102 Cohort 3 | Experimental | Drug: GTX-10220 mg starting dose followed by intra-patient dose escalation up to 55 mg and then a maintenance phase (in U.S participants 4 to <17 years of age) |
| GTX-102 Cohort 4 | Experimental | Drug: GTX-1023.3 mg starting dose followed by slow intra-patient dose escalation up to 5 mg and then a maintenance phase (in Ex-U.S participants 4 to <8 years of age) |
| GTX-102 Cohort 5 | Experimental | Drug: GTX-1025 mg starting dose followed by slow intra-patient dose escalation up to 7.5 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Cohort 6 | Experimental | Drug: GTX-1027.5 mg starting dose followed by slow intra-patient dose escalation up to 10 mg and then a maintenance phase (in Ex-U.S participants 4 to <8 years of age) |
| GTX-102 Cohort 7 | Experimental | Drug: GTX-10210 mg starting dose followed by slow intra-patient dose escalation up to 12 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Cohort US | Experimental | Drug: GTX-1022 mg for 4 monthly doses followed by a quarterly maintenance regimen |
| GTX-102 Expanded Enrollment Cohort A | Experimental | Drug: GTX-102Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants 4 to <8 years of age) |
| GTX-102 Expanded Enrollment Cohort B | Experimental | Drug: GTX-102Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Expanded Enrollment Cohort C | Experimental | Drug: GTX-102Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants 4 to <8 years of age) |
| GTX-102 Expanded Enrollment Cohort D | Experimental | Drug: GTX-102Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Cohort E | Experimental | Drug: GTX-102Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in participants that transition from GTX-102 US Cohort only) |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Signed informed consent from parent(s) or legal guardian(s)
- Documented genetic confirmation of full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13 including class I, II or III
- Stable seizure control (defined as clinically stable with no changes in antiepileptic medications over the prior 1 month before the screening visit, other than weight associated dose adjustments)
- Able to ambulate independently, or with an assistive device (note, a child whose primary means of mobility is by wheelchair is excluded from the study)
- Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time within 1.2 x the normal limits
Key exclusion criteria (13 listed)
- Any change in medications (excluding AEDs) or diet/supplements intended to treat symptoms of AS (eg, sleeping aids, supplements, dietary change including ketogenic or low-glycemic index diet, other) over the prior 1 month before screening
- Any bleeding or platelet disorder
- Any clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurological, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, make the patient unsuitable for participation in, and/or unable to complete the study procedures
- Any laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study result
- Known positive for hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GTX-102antisense oligonucleotide | Drug | GTX-102 Cohort 1, GTX-102 Cohort 2, GTX-102 Cohort 3, GTX-102 Cohort 4, GTX-102 Cohort 5, GTX-102 Cohort 6, GTX-102 Cohort 7, GTX-102 Cohort E, GTX-102 Cohort US, GTX-102 Expanded Enrollment Cohort A, GTX-102 Expanded Enrollment Cohort B, GTX-102 Expanded Enrollment Cohort C, GTX-102 Expanded Enrollment Cohort D |
Primary outcome
Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), Adverse Events of Special Interest (AESIs), AEs Leading to Discontinuation and Severity of AEs
Time frame: Up to Day 337
1 secondary outcome
Pharmacokinetics of GTX-102 over time
Time frame: Up to Day 337
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Derived from this study: PubMed 36947593Dindot SV, Christian S, Murphy WJ, Berent A, Panagoulias J, Schlafer A, Ballard J, Radeva K, Robinson R, Myers L, Jepp T, Shaheen H, Hillman P, Konganti K, Hillhouse A, Bredemeyer KR, Black L, Douville J; FIRE consortium; FIRE Consortium. An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the UBE3A-AS transcript. Sci Transl Med. 2023 Mar 22;15(688):eabf4077. doi: 10.1126/scitranslmed.abf4077. Epub 2023 Mar 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
25 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GTX-102 in people with Angelman Syndrome, run by Ultragenyx Pharmaceutical Inc at 25 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Canada, Australia, Spain, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), Adverse Events of Special Interest (AESIs), AEs Leading to Discontinuation and Severity of AEs (time frame: Up to Day 337). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04259281, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.