A Phase 2, Open-label, Basket Study Investigating the Safety and Efficacy of GTX-102 in Adult and Pediatric Subjects with Deletion- or Nondeletion-type Angelman Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 19
- 试验地点
- 7
- 主要终点
- All Subprotocols - Primary Safety Endpoint: TEAEs and SAEs, frequency, severity, and relationship to investigational product, procedure, and premedication throughout the study.
研究概览
简要总结
Primary Safety Objective: evaluate the safety of GTX-102. Primary Efficacy Objective: evaluate the efficacy of GTX-102.
研究设计
- 分配方式
- Randomized
- 主要目的
- Control Period
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent from parent(s) or legal guardian(s)
- •Males and females of the following ages and genotypes at time of informed consent: a. Subprotocol A: ≥ 1 to < 4 years of age with a genetically confirmed diagnosis of deletion-type Angelman Syndrome b. Subprotocol B: ≥ 4 to < 18 years of age with a genetically confirmed diagnosis of UPD/ICD Angelman Syndrome c. Subprotocol C: ≥ 18 to < 65 years of age with a genetically confirmed diagnosis of Angelman Syndrome, any genotype d. Subprotocol D: ≥ 4 to < 18 years of age with a genetically confirmed diagnosis of mutation-type Angelman Syndrome.
- •Weight ≥ 8 kg at Screening Visit.
- •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.
- •Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, and all study procedures, including LP procedure, MRI, and tolerating anesthesia without intubation.
- •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.
排除标准
- •Any change in medications or diet/supplements intended to treat symptoms of AS (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).
- •Any condition that creates an increased risk of unsuccessful LP.
- •Current or expected concomitant use of drugs that increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors).
- •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.
- •Presence or history of any condition, lab abnormality, or infection that, in the judgement of the Investigator, would interfere with study participation, pose undue safety risk, or would confound interpretation of results.
- •Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study.
- •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.
- •Concurrent participation in any interventional study.
结局指标
主要结局
All Subprotocols - Primary Safety Endpoint: TEAEs and SAEs, frequency, severity, and relationship to investigational product, procedure, and premedication throughout the study.
All Subprotocols - Primary Safety Endpoint: TEAEs and SAEs, frequency, severity, and relationship to investigational product, procedure, and premedication throughout the study.
Subprotocol GTX-102-CL210A - Primary Efficacy Endpoint: Bayley-4 Cognitive raw score without caregiver input, change from Baseline at Day 338.
Subprotocol GTX-102-CL210A - Primary Efficacy Endpoint: Bayley-4 Cognitive raw score without caregiver input, change from Baseline at Day 338.
Subprotocol GTX-102-CL210B - Primary Efficacy Endpoint: MDRI Net response at Day 338, with the following domains - assessments: Cognition - Bayley-4 Cognitive raw score, Communication - Bayley-4 Receptive Communication raw score, Behavior - ABC-C Hyperactivity/Noncompliance, Sleep - ASA Sleep rating, Motor Function - ASA Gross Motor rating.
Subprotocol GTX-102-CL210B - Primary Efficacy Endpoint: MDRI Net response at Day 338, with the following domains - assessments: Cognition - Bayley-4 Cognitive raw score, Communication - Bayley-4 Receptive Communication raw score, Behavior - ABC-C Hyperactivity/Noncompliance, Sleep - ASA Sleep rating, Motor Function - ASA Gross Motor rating.
Subprotocol GTX-102-CL210C - Primary Efficacy Endpoint: MDRI Net response at Day 338, with the following domains - assessments: Expressive Communication - Vineland-3 Expressive Communication raw score, Receptive Communication – Vineland-3 Receptive Communication raw score, Behavior - ABC-C Irritability subscale score, Motor Function - ASA Gross Motor rating.
Subprotocol GTX-102-CL210C - Primary Efficacy Endpoint: MDRI Net response at Day 338, with the following domains - assessments: Expressive Communication - Vineland-3 Expressive Communication raw score, Receptive Communication – Vineland-3 Receptive Communication raw score, Behavior - ABC-C Irritability subscale score, Motor Function - ASA Gross Motor rating.
Subprotocol GTX-102-CL210D - Primary Efficacy Endpoint: MDRI Net response at TxD 338, with the following domains - assessments: Cognition - Bayley-4 Cognitive raw score, Communication - Bayley-4 Receptive Communication raw score, Behavior - ABC-C Hyperactivity/Noncompliance, Sleep - ASA Sleep rating, Motor Function - ASA Gross Motor rating.
Subprotocol GTX-102-CL210D - Primary Efficacy Endpoint: MDRI Net response at TxD 338, with the following domains - assessments: Cognition - Bayley-4 Cognitive raw score, Communication - Bayley-4 Receptive Communication raw score, Behavior - ABC-C Hyperactivity/Noncompliance, Sleep - ASA Sleep rating, Motor Function - ASA Gross Motor rating.
次要结局
- Subprotocol GTX-102-CL210A - Change from Baseline at Day 338 in: Bayley-4 Receptive Communication raw score, Bayley-4 Gross Motor raw score
- Subprotocol GTX-102-CL210B - Change from Baseline at Day 338 in: Bayley-4 Cognitive raw score, Bayley-4 Receptive Communication raw score, Vineland-3 Receptive Communication raw score, Vineland-3 Expressive Communication raw score, ABC-C Hyperactivity/Noncompliance subscale score, ASA Sleep rating, ASA Gross Motor rating, Bayley-4 Gross Motor raw score.
- Subprotocol GTX-102-CL210C - Change from Baseline at Day 338 in: Vineland-3 Receptive Communication raw score, Vineland-3 Expressive Communication raw score, ABC-C Irritability subscale score, ASA Gross Motor rating.
- Subprotocol GTX-102-CL210D - Change from Baseline (or pretreatment) at TxD 338: Bayley-4 Cognitive raw score, Bayley-4 Receptive Communication raw score, Vineland-3 Receptive Communication raw score, Vineland-3 Expressive Communication raw score, ABC-C Hyperactivity/Noncompliance subscale score, ASA Sleep rating, ASA Gross Motor rating, Bayley-4 Gross Motor raw score.
研究者
Medical Information
Scientific
Ultragenyx Pharmaceutical Inc.