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

Angelman Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04259281
• Other study ID #: GTX-102-001
• Secondary ID: 2021-001793-36
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 24, 2020
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Angelman Syndrome
• Syndrome

Intervention

Drug:
• GTX-102
antisense oligonucleotide

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg	Victoria
Australia	The Royal Children's Hospital	Parkville	Victoria
Australia	Queensland Children's Hospital	South Brisbane
Canada	MAGIC Clinic Ltd	Calgary	Alberta
Canada	Children's Hospital of Western Ontario	London	Ontario
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
France	Hopital de la Timone	Marseille
France	AP-HP Hopital Necker-Enfants Malades	Paris
Germany	Universitatsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Israel	The Edmond and Lily Safra Children's Hospital	Ramat Gan
Spain	Hospital Sant Joan de Deu	Esplugues De Llobregat	Barcelona
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Universitari Parc Tauli	Sabadell	Barcelona
United Kingdom	Cambridge University Hospitals	Cambridge
United Kingdom	Great Ormond Street Hospital for Children	London
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United States	Rare Disease Research	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	UCLA Medical Center	Los Angeles	California
United States	Weill Cornell Medicine	New York	New York
United States	Rady Children's Hospital	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), Adverse Events of Special Interest (AESIs), AEs Leading to Discontinuation and Severity of AEs		Up to Day 337
Secondary	Pharmacokinetics of GTX-102 over time	Maximum drug concentration (Cmax)	Up to Day 337