A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome

NCT ID: NCT04259281

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-24
• Study Completion Date: 2025-01-08

Brief 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).

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GTX-102 Cohort 1

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort 2

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort 3

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort 4

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort 5

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort 6

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort 7

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort US

2 mg for 4 monthly doses followed by a quarterly maintenance regimen

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Expanded Enrollment Cohort A

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Expanded Enrollment Cohort B

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Expanded Enrollment Cohort C

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Expanded Enrollment Cohort D

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

GTX-102 Cohort E

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)

Group Type: EXPERIMENTAL

GTX-102

Intervention Type: DRUG

antisense oligonucleotide

Interventions

GTX-102

antisense oligonucleotide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)
• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

UCLA Medical Center

Los Angeles, California, United States

Rady Children's Hospital

San Diego, California, United States

Rare Disease Research

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Weill Cornell Medicine

New York, New York, United States

Austin Health

Heidelberg, Victoria, Australia

The Royal Children's Hospital

Parkville, Victoria, Australia

Queensland Children's Hospital

South Brisbane, , Australia

MAGIC Clinic Ltd

Calgary, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Children's Hospital of Western Ontario

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Hopital de la Timone

Marseille, , France

AP-HP Hopital Necker-Enfants Malades

Paris, , France

Universitatsklinikum Leipzig

Leipzig, Saxony, Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

The Edmond and Lily Safra Children's Hospital

Ramat Gan, , Israel

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, Spain

Hospital Universitari Parc Tauli

Sabadell, Barcelona, Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Cambridge University Hospitals

Cambridge, , United Kingdom

Great Ormond Street Hospital for Children

London, , United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Israel; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36947593 (View on PubMed)

Other Identifiers

2021-001793-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GTX-102-001

Identifier Type: -

Identifier Source: org_study_id