A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS)
Purpose
The main goal of the study is to evaluate the safety and efficacy of GTX-102 in participants with Angelman syndrome.
Condition
- Angelman Syndrome
Eligibility
- Eligible Ages
- Between 1 Year and 64 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Signed informed consent from parent(s) or legal guardian(s) 2. Males and females of the following ages and genotypes at time of informed consent: 1. Subprotocol A: ≥ 1 to < 4 years of age with a genetically confirmed diagnosis of deletion-type Angelman syndrome 2. Subprotocol B: ≥ 4 to < 18 years of age with a genetically confirmed diagnosis of UPD/ICD Angelman syndrome 3. Subprotocol C: ≥ 18 to < 65 years of age with a genetically confirmed diagnosis of Angelman syndrome, any genotype 4. Subprotocol D: ≥ 4 to < 18 years of age with a genetically confirmed diagnosis of mutation-type Angelman syndrome 3. Weight ≥ 8 kg at Screening Visit 4. Platelet count, prothrombin time / international normalized ratio, and partial thromboplastin time < 1.5x the upper limit of normal and platelets > 75,000 cells/mm3 at the Screening Visit 5. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, and all study procedures, including lumbar puncture (LP) procedure, magnetic resonance imaging (MRI) and tolerating anesthesia without intubation 6. From the time of informed consent through to at least 6 months after the final dose of GTX-102, females of childbearing potential who are sexually active must use highly effective contraception or abstinence. Males are able to participate if they agree to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the study and for at least 3 months after the final dose of GTX-102
Exclusion Criteria
- Any change in medications or diet/supplements intended to treat symptoms of Angelman Syndrome (eg, sleeping aids, antiseizure medications, supplements, dietary change including ketogenic or low-glycemic index diet, other) within the month prior to the Screening Visit (excluding weight-based adjustments) 2. Any condition that creates an increased risk of unsuccessful lumbar puncture 3. Current or expected concomitant use of drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors) 4. Known hypersensitivity to GTX-102 or its excipients or required premedication that, in the judgment of the Investigator, places the subject at increased risk for adverse effects 5. Presence or history of any condition, lab abnormality, or infection that, in the judgment of the Investigator, would interfere with study participation, pose undue safety risk, or would confound interpretation of results 6. Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study 7. Use of any investigational product or investigational medical device within 6 months or 5 half-lives prior to the Screening Visit, or any prior use of gene therapy or an ASO regardless of length of time since last use 8. Concurrent participation in any interventional study
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Subprotocol A GTX-102 |
Participants with deletion-type Angelman syndrome, ≥1 to <4 years of age will receive increasing doses of GTX-102 via intrathecal (IT) injection until the target dose is achieved. Dosing occurs every 3 months (Q3M) thereafter. |
|
|
Experimental Subprotocol B GTX-102 |
Participants with paternal uniparental disomy (UPD)/imprinting center defect (ICD) Angelman syndrome, ≥4 to <18 years of age will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
|
|
Experimental Subprotocol C GTX-102 |
Participants with all genotypes of Angelman syndrome, ≥18 to <65 years of age will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
|
|
Experimental Subprotocol D GTX-102 |
Participants with mutation-type Angelman syndrome, ≥4 to <18 years of age will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
|
|
Experimental Subprotocol D No Intervention then GTX-102 |
Participants with mutation-type Angelman syndrome, ≥4 to <18 years of age will receive no treatment during the initial period. At the end of the no treatment period, participants will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
|
Recruiting Locations
Rush University Medical Center
Chicago 4887398, Illinois 4896861 60612
Chicago 4887398, Illinois 4896861 60612
Rare Disease Research
Hillsborough 4471241, North Carolina 4482348 27278
Hillsborough 4471241, North Carolina 4482348 27278
Akron Children's Hospital
Akron 5145476, Ohio 5165418 44308
Akron 5145476, Ohio 5165418 44308
Carum Research Inc.
Dallas 4684888, Texas 4736286 75243
Dallas 4684888, Texas 4736286 75243
More Details
- Status
- Recruiting
- Sponsor
- Ultragenyx Pharmaceutical Inc
Detailed Description
This basket study is designed to evaluate safety and efficacy of GTX-102 in participants with Angelman syndrome across genotypes and age groups. The study consists of subprotocols A, B, C and D. All subprotocols are open-label and follow the same design which includes a Screening, Loading and Maintenance period. Subprotocols A, B and C are single arm only. In subprotocol D, participants are randomized 2:1 to a GTX-102 group or a No Treatment group. The No Treatment group follows the same schedule of events as all other groups after completion of the No Treatment period. Participants from all the subprotocols have the option to continue treatment in a long-term extension study following their end of study visit.