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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04259281




Registration number
NCT04259281
Ethics application status
Date submitted
31/01/2020
Date registered
6/02/2020
Date last updated
5/08/2024

Titles & IDs
Public title
A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome
Scientific 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)
Secondary ID [1] 0 0
2021-001793-36
Secondary ID [2] 0 0
GTX-102-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Angelman Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GTX-102

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: GTX-102 Cohort US - 2 mg for 4 monthly doses followed by a quarterly maintenance regimen

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: 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)

Experimental: 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)


Treatment: Drugs: GTX-102
antisense oligonucleotide
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), Adverse Events of Special Interest (AESIs), AEs Leading to Discontinuation and Severity of AEs
Timepoint [1] 0 0
Up to Day 337
Secondary outcome [1] 0 0
Pharmacokinetics of GTX-102 over time
Timepoint [1] 0 0
Up to Day 337

Eligibility
Key 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
Minimum age
4 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
74
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment hospital [2] 0 0
The Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
QLD 4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
Germany
State/province [12] 0 0
Sachsen
Country [13] 0 0
Germany
State/province [13] 0 0
Hamburg
Country [14] 0 0
Israel
State/province [14] 0 0
Ramat Gan
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Cambridge
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ultragenyx Pharmaceutical Inc
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT04259281
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Ultragenyx Pharmaceutical Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04259281