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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04259281
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : July 29, 2022
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Description
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Brief Summary:
The primary objective of the study is to evaluate the safety and tolerability of multiple-ascending doses of GTX-102 administered by IT injection to patients with AS.

Condition or disease Intervention/treatment Phase
Angelman Syndrome Drug: GTX-102 Phase 1 Phase 2

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 patients with AS.

The study includes a monthly dosing period followed by a maintenance period. The duration of study for each patient in the dose escalation phase is anticipated to be approximately 5 months. Patients will then transition to a maintenance period of study where they may receive continued treatment with GTX-102.

This study was previously posted by GeneTX Biotherapeutics, LLC and was transferred to Ultragenyx in July 2022.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 83 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 24, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: GTX-102 Cohort 4
3.3 mg for 3-4 monthly doses followed by a quarterly maintenance regimen
 Drug: GTX-102
antisense oligonucleotide
Experimental: GTX-102 Cohort 5
5 mg for 3-4 monthly doses followed by a quarterly maintenance regimen
 Drug: GTX-102
antisense oligonucleotide
Experimental: GTX-102 Cohort 6
7.5 mg for 3-4 monthly doses followed by a quarterly maintenance regimen
 Drug: GTX-102
antisense oligonucleotide
Experimental: GTX-102 Cohort 7
10 mg for 3-4 monthly doses followed by a quarterly maintenance regimen
 Drug: GTX-102
antisense oligonucleotide
Experimental: GTX-102 US Cohort
2 mg for 4 monthly doses followed by a quarterly maintenance regimen
 Drug: GTX-102
antisense oligonucleotide


Outcome Measures
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Primary Outcome Measures :
  1. Safety: incidence of adverse events [ Time Frame: Up to Day 128 ]
    Number of patients with adverse events (AEs)

  2. Safety: incidence of serious adverse events [ Time Frame: Up to Day 128 ]
    Number of patients with serious adverse events (SAEs)

  3. Safety: severity of adverse events [ Time Frame: Up to Day 128 ]
    Severity of AEs


Secondary Outcome Measures :
  1. Pharmacokinetics of GTX-102 [ Time Frame: Day 2, Day 3, Day 4, Day 30, Day 58, Day 86, Day 100/128 ]
    Maximum drug concentration (Cmax)


Eligibility Criteria
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Ages Eligible for Study:   4 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent from parent(s) or legal guardian(s)
  • Documented genetic confirmation of full maternal UBE3A gene deletion causing AS (e.g. DNA methylation testing with either a chromosomal microarray or FISH) in the region of 15q11.2-q13 including class I, II or III).
  • Age ≥ 4 to ≤ 17 years at screening (in US Age ≥ 4 to < 8 years at screening)
  • Stable seizure control (defined as clinically stable with no changes in antiepileptic medications over the prior 1 month before screening visit, other than weight associated dose adjustments)
  • Platelet count, prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits
  • Normal renal function with serum creatinine and spot urine protein within normal limits
  • Normal hepatic function with total bilirubin, aspartate aminotransferase (AST),alanine aminotransferase (ALT) and alkaline phosphatase within normal limits
  • Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures LP.
  • Able to tolerate the anesthetic regimen required for LP procedure

Exclusion Criteria:

  • Any change in medications (excluding antiepileptic drugs) or diet intended to treat symptoms of AS (e.g. sleeping aids, supplements, ketogenic or low-glycemic index diet, other) over the prior 1 month before screening.
  • Inability to ambulate independently or with an assistive device or caregiver hand-hold
  • Any bleeding or platelet disorder
  • Any clinically significant (CS) cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, will 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
  • 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 (e.g. heparin, low molecular weight heparin, platelet inhibitors).
  • Use of any investigational oligonucleotide in the past 6 months (with the exception of GTX-102)
  • Any prior use of gene therapy
  • Use of any investigational drugs in the past 6 months (with the exception of GTX-102)
  • Any medical condition that would require intubation for the anesthesia procedure
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04259281


Contacts
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Contact: Patients Contact: Trial Recruitment 1-888-756-8657 trialrecruitment@ultragenyx.com
Contact: HCPs Contact: Medical Information 1-888-756-8657 medinfo@ultragenyx.com

Locations
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United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Barbara Leane       Barbara_Leane@rush.edu   
Canada, Ontario
Children's Hospital of Western Ontario Recruiting
London, Ontario, Canada
Contact: Rhiannon Hicks       rhiannon.hicks@lhsc.on.ca   
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Erick Sell, MD       esell@cheo.on.ca   
Canada, Quebec
McGill University Health Centre Recruiting
Montréal, Quebec, Canada
Contact: Freqerique Arnaud       Frederique.Arnaud@MUHC.MCGILL.CA   
United Kingdom
Cambridge University Hospitals Recruiting
Cambridge, United Kingdom
Contact: Kay Lilley       kay.lilley@addenbrookes.nhs.uk   
Great Ormond Street Hospital for Children Recruiting
London, United Kingdom
Contact: Helen Cross, MD       Helen.Cross@gosh.nhs.uk   
Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, United Kingdom, OX3 7LE
Contact: Laurent Servais, MD PhD       laurent.servais@paediatrics.ox.ac.uk   
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
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Study Director: Medical Director Ultragenyx Pharmaceutical Inc
More Information
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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT04259281    
Other Study ID Numbers: GTX-102-001
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: July 29, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Angelman Syndrome
Syndrome
Disease
Pathologic Processes
Movement Disorders
Central Nervous System Diseases
 Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn