NCT04259281

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).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
74

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2020

Longer than P75 for phase_1

Geographic Reach
8 countries

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 31, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 6, 2020

Completed
18 days until next milestone

Study Start

First participant enrolled

February 24, 2020

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 8, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 8, 2025

Completed
Last Updated

January 9, 2026

Status Verified

January 1, 2026

Enrollment Period

4.9 years

First QC Date

January 31, 2020

Last Update Submit

January 5, 2026

Conditions

Angelman Syndrome

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • Pharmacokinetics of GTX-102 over time

    Up to Day 337

Study Arms (13)

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)

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)

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)

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)

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)

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)

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)

Drug: GTX-102

GTX-102 Cohort US

EXPERIMENTAL

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

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)

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)

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)

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)

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)

Drug: GTX-102

Interventions

GTX-102DRUG

antisense oligonucleotide

GTX-102 Cohort 1GTX-102 Cohort 2GTX-102 Cohort 3GTX-102 Cohort 4GTX-102 Cohort 5GTX-102 Cohort 6GTX-102 Cohort 7GTX-102 Cohort EGTX-102 Cohort USGTX-102 Expanded Enrollment Cohort AGTX-102 Expanded Enrollment Cohort BGTX-102 Expanded Enrollment Cohort CGTX-102 Expanded Enrollment Cohort D

Eligibility Criteria

Age4 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Rare Disease Research

Atlanta, Georgia, 30318, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Queensland Children's Hospital

South Brisbane, QLD 4101, Australia

Location

MAGIC Clinic Ltd

Calgary, Alberta, T2E 7Z4, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H3V4, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

McGill University Health Centre

Montreal, Quebec, Canada

Location

Hopital de la Timone

Marseille, France

Location

AP-HP Hopital Necker-Enfants Malades

Paris, 75015, France

Location

Universitatsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

The Edmond and Lily Safra Children's Hospital

Ramat Gan, Israel

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, Spain

Location

Hospital Universitari Parc Tauli

Sabadell, Barcelona, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Location

Cambridge University Hospitals

Cambridge, United Kingdom

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 36947593DERIVED

MeSH Terms

Conditions

Angelman Syndrome

Condition Hierarchy (Ancestors)

Movement DisordersCentral Nervous System DiseasesNervous System DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesChromosome DisordersGenetic Diseases, InbornImprinting Disorders

Study Officials

  • Medical Director

    Ultragenyx Pharmaceutical Inc

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 31, 2020

First Posted

February 6, 2020

Study Start

February 24, 2020

Primary Completion

January 8, 2025

Study Completion

January 8, 2025

Last Updated

January 9, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

GB(3)ES(3)AU(3)FR(2)US(6)CA(5)DE(2)IL(1)