A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome
Angelman Syndrome
About this trial
This is an interventional treatment trial for Angelman Syndrome
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 (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
Sites / Locations
- Rare Disease ResearchRecruiting
- Rush University Medical Center
- Boston Children's HospitalRecruiting
- Austin Health
- The Royal Children's Hospital
- Queensland Children's Hospital
- MAGIC Clinic Ltd
- British Columbia Children's Hospital
- Children's Hospital of Western Ontario
- Children's Hospital of Eastern Ontario
- McGill University Health Centre
- Hopital de la Timone
- AP-HP Hopital Necker-Enfants Malades
- Universitatsklinikum Leipzig
- Universitatsklinikum Hamburg-Eppendorf
- The Edmond and Lily Safra Children's Hospital
- Hospital Sant Joan de DeuRecruiting
- Hospital Universitari Parc TauliRecruiting
- Hospital Universitario Puerta de HierroRecruiting
- Cambridge University Hospitals
- Great Ormond Street Hospital for Children
- Oxford University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
GTX-102 Cohort 1
GTX-102 Cohort 2
GTX-102 Cohort 3
GTX-102 Cohort 4
GTX-102 Cohort 5
GTX-102 Cohort 6
GTX-102 Cohort 7
GTX-102 Cohort US
GTX-102 Expanded Enrollment Cohort A
GTX-102 Expanded Enrollment Cohort B
GTX-102 Expanded Enrollment Cohort C
GTX-102 Expanded Enrollment Cohort D
GTX-102 Cohort E
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)
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)
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)
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)
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)
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)
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)
2 mg for 4 monthly doses followed by a quarterly maintenance regimen
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)
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)
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)
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)
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)