A study of the safety of GTX-102 in pediatric patients with Angelman Syndrome (AS)

Phase 1

Conditions: Angelman Syndrome
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2021-001793-36-DE

Lead Sponsor: ltragenyx Pharmaceutical Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 67

Inclusion Criteria

1. Signed informed consent from parent(s) or legal guardian(s)
2. Documented genetic confirmation of full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13 including class I, II or III)
3. Age 4 to 17 years inclusive at screening
4. 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)
5. 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)
6. Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time within 1.2 x the normal limits
7. Normal renal function with serum creatinine and spot urine protein = 1.4 x ULN
8. 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 AEDs or Gilbert syndrome
9. Willing and able to comply with scheduled visits, drug administration plan, laboratory
tests, study restrictions, and all study procedures, including LP procedure.
10. Able to tolerate the anesthetic regimen, if required for LP procedure
11. a) 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
b) 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 67
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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.
2. Any bleeding or platelet disorder
3. Any clinically significant 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.
4. 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
5. Known positive for hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
6. Any active infection
7. Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
8. Drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors).
9. Any prior use of gene therapy
10. 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)
11. Known hypersensitivity to any oligonucleotide, as demonstrated by an immunemediated
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
12. Patient is pregnant or lactating
13. Any medical condition that would require intubation for the anesthesia procedure