2024-512637-32-00招募中3 期
ASPIRO: A Phase 1/2/3, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Efficacy of AT132, an AAV8-Delivered Gene Therapy in X-Linked Myotubular Myopathy (XLMTM) Patients
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Primary Efficacy Endpoint: • Change from baseline in hours of ventilation support at Week 24
研究概览
简要总结
-
To determine the therapeutic dose of AT132
-
To confirm the safety and efficacy of the therapeutic dose of AT132
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Subject has a diagnosis of XLMTM resulting from a genetically confirmed mutation in the MTM1 gene as assessed by a Sponsor- approved testing facility.* * = Inclusion/exclusion criteria for delayed treatment control subjects before receiving AT
- •Subject is male.*
- •Subject is aged less than 5 years old at dosing*
- •Subject requires mechanical ventilatory support: Part 1: Subject requires some mechanical ventilatory support (eg., ranging from 24 hours per day full time mechanical ventilation, to noninvasive support such as continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP] during sleeping hours). Part 2: Subject requires invasive mechanical ventilatory support ranging from 20 to 24 hours per day at screening (confirmed by daytime polysomnographic study).
- •Subject requiring invasive mechanical ventilator support is fitted with or willing to be fitted with a cuffed tracheostomy tube for some respiratory assessments.*
- •Subject has ventilator maximum positive end-expiratory pressure (PEEP) < 8 cm H2O at screening.*
- •Signed informed consent by the parent(s) or legally authorized representative(s) (LAR) (when applicable).*
- •Subject and parent(s)/LAR(s) are willing and able to comply with study visits and study procedures.*
- •Subject's range is ≥ 4.8 kg (UNIQUE to France)
排除标准
- •Subject is participating in an interventional study designed to treat XLMTM.* * = If a subject is a delayed-treatment control, this inclusion/exclusion criterion must be met before receiving AT
- •10.Subject has a contraindication to prednisolone.*
- •11.Subject has a contraindication to study drug or ingredients.*
- •Subject has previous scoliosis repair surgery/procedure, or planned/expected scoliosis repair surgery/procedure, in the 12 months following Day 1 (Part 2 including any subjects enrolles under protocol v8 and beyond ).
- •Subject has contractures, scoliosis, or other medical condition that would limit the potential to achieve unassisted sitting, in the opinion of the Investigator (Part 2 including any subjects enrolles under protocol v8 and beyond ).
- •Subject is able to sit without assistance for at least 30 seconds at screening, in the opinion of the Investigator (Part 2 including any subjects enrolles under protocol v8 and beyond ).
- •Subject has a clinically important condition, including CTCAE v4.03 Grade ≥ 2 anemia (< 10 g/dL hemoglobin).*
- •Subject has a contraindication to ursodiol (ursodeoxycholic acid).*
- •Subject has a prior diagnosis or history of cardiac arrhytmias, myocarditis, or any other cardiac disease (UNIQUE to FRANCE).
- •Subject has a contradiction to general anesthesia and to muscle biopsy procedure (UNIQUE to France).
- •Subject born < 35 weeks gestation who is still not term as per corrected age.
- •Subject tests positive for AAV8 neutralizing antibody with titers > 1:20 (subjects under the age of 18 months may be retested in cases where antibodies may have been maternally acquired and titers may decline in the first months of life).*
- •Subject had recent surgery (< 3 months before Day 1) or has planned surgery that may confound data collection during the first 48 weeks of the study.
- •Subject has a clinically important condition or life-threatening disease, other than XLMTM, in the opinion of the Investigator.*
- •Subject has a clinically significant underlying liver disease, defined as: • ≥ Grade 3 aspartate aminotransferase (AST) (> 5.0 x upper limit of normal [ULN]; Common Terminology Criteria for Adverse Events [CTCAE] v. 4.03)* • ≥ Grade 3 alanine aminotransferase (ALT) (> 5.0 x ULN; CTCAE v. 4.03)* • Hepatic peliosis or any other clinically significant structural abnormality detected by ultrasound*
- •Subject is currently experiencing a clinically important respiratory infection or other active infection.*
- •8.Subject has received pyridostigmine or any medication to treat XLMTM within 3 months before Day 1.*
- •9.Other than as required per protocol, subject has received immunemodulating agents within 3 months before Day 1 (use of inhaled corticosteroids to manage chronic respiratory conditions is allowed); use of other concomitant medications to manage chronic conditions must have beenstable for at least 4 weeks before dosing.*
结局指标
主要结局
Primary Efficacy Endpoint: • Change from baseline in hours of ventilation support at Week 24
Primary Efficacy Endpoint: • Change from baseline in hours of ventilation support at Week 24
次要结局
- Key Secondary Efficacy Endpoint: Percentage of subjects achieving functionally independent sitting for at least 30 seconds at Week 24
- Other Secondary Efficacy Endpoints: • Time to reduction in required ventilator support to ≤ 16 hours a day (only in subjects who require invasive ventilation) at Week 24
- • Change from baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) at Week 24
- • Change from baseline in maximal inspiratory pressure (MIP) at Week 24
- • Change from baseline in quantitative analysis of myotubularin expression in the muscle biopsy at Week 24
- • Change from baseline in quality of life assessments at Week 24 (ie, the Assessment of Caregiver Experience with Neuromuscular Disease [ACEND] and Pediatric Quality of Life Inventory [PedsQL])
- • Number (%) of age-appropriate clinically relevant gross motor function milestones attained through Week 24
- • Percentage of subjects achieving full ventilator independence at Week 24
- •Survival
- 10 Safety Endpoints: • Adverse events (AEs), serious AEs (SAEs), and findings from safety laboratory tests, 12-lead ECG, echocardiograms (ECHOs), vital signs, growth parameters, physical examinations, liver ultrasounds, antibody formation (anti AAV8, anti MTM1), viral shedding , annualized hospitalization rate , annualized respiratory and non-respiratory SAE rate, and length of stay per hospitalization
研究者
Clinical Trial Unit Head
Scientific
Astellas Gene Therapies Inc.
研究点 (2)
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