2023-506440-16-00招募中2 期
A Phase I/II, open-label, dose escalation study to evaluate the safety of 2 doses of intravenous ATA-200, an adeno-associated viral vector carrying the human gamma-sarcoglycan gene, in patients with gamma-sarcoglycanopathy (limb-girdle muscular dystrophy LGMDR5, formerly LGMD2C).
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- incidence of AEs recording throughout the study
研究概览
简要总结
to assess the safety and tolerability of intravenous administration ATA-200 in pediatric ambulant patients with LGMDR5 at two different dosage levels and to select the recommended dose for future studies.
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Part 2: Long-Term Follow-up for additional 4.5 years
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Ambulant male or female patients at least 6 and less than 12 years of age at screening
- •Confirmed LGMDR5 diagnosis before age of 10, based on clinical presentation and genotyping identifying the SGCG gene mutations
- •Able to Perform the 10-meter walk test (10MWT) within 15 sec without help, such as cane, or bilateral help, such as elbow crutches or orthotic devices below the knees and to rise from a standard-height chair with or without arm support
- •Signed written informed consent before any study related procedure is performed
- •Patient medical status sufficiently stable and ability of patient and parents/legal guardian, in the opinion of the investigator, to adhere to the study visits schedule and other protocol requirements.
- •Seronegative patients for neutralizing antibodies against AAV8
排除标准
- •Previous participation in gene and cell therapy trials
- •Inability to cooperate with muscle testing or to perform respiratory function tests
- •Presence or history of concomitant muscular or other medical condition that might interfere with LGMDR5 evolution or that would confound scientific rigor or interpretation of results, e.g., current infectious episode (pulmonary, ENT, etc.), abnormal laboratory test if clinically significant
- •Current or history of significant heart, lung, hepato-biliary or renal disease or impairment that jeopardize the safety of the subject according to the investigator
- •Acute illness within 4 weeks of the anticipated IMP administration which may interfere with study assessments
- •Current participation in a clinical trial of another investigational medicinal product
- •Any condition that would contraindicate treatment with immunosuppressant therapy
- •Presence of any permanent items (e.g., metal braces) precluding undergoing MRI
- •Any vaccination 1 month prior to the planned IMP administration
- •Serology consistent with HIV exposure or active hepatitis B or C infection
- •Grade 2 or higher lab abnormalities for LFT (except isolated AST increase), bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT, and a PTT, according to current version of CTCAE. Isolated AST increase associated with CK levels > 800 U/L, ALT < 2 x ULN, and GLDH within normal range, is not exclusionary.
- •Known hypersensitivity to IMP excipients, to eculizumab, murine proteins, or any excipients in eculizumab formulation, and to contrast media
- •Cardiomyopathy based on physical and cardiological examination and echocardiography with Left Ventricular Ejection Fraction (LVEF) below 50%
- •Any respiratory assistance, including non-invasive daytime or nocturnal ventilation
结局指标
主要结局
incidence of AEs recording throughout the study
incidence of AEs recording throughout the study
incidence of clinically relevant abnormalities detection in vital signs
incidence of clinically relevant abnormalities detection in vital signs
physical examination findings
physical examination findings
vital signs
vital signs
myalgia assessment
myalgia assessment
cardiac assessment
cardiac assessment
laboratory determinations
laboratory determinations
次要结局
- Efficacy: muscle Function Tests: North Star Assessment for Neuromuscular Disorders (NSAD) and Performance of the Upper Limb (PUL)
- Efficacy: timed Function Tests: 10-meter walk test (10MWT); 100-Meter Walk Test (100MWT); Time to Rise From Floor (RFF); 4-Stair climb test
- Efficacy: muscle Strength Tests: Myotools and Hand Held Dynamometry (HHD)
- Efficacy: Patient reported outcome and QoL: Change in video outcomes capturing disease hallmarks
- Efficacy: Imaging Assessments: Muscle Nuclear Magnetic Resonance Imaging (NMRI) and spectroscopy: quantitative NMRI (including fat-water separation, based MRI and NMRS) in the lower limbs
- Efficacy: Respiratory assessments: Pulmonary function tests, including forced vital capacity (FVC), minimal inspiratory/expiratory pressure (MIP/MEP), sniff nasal inspiratory pressure (SNIP) test
- Efficacy: Respiratory assessments: Respiratory questionnaire
- Efficacy: Muscle Biopsy: Histological assessment, including centronucleation index and fibrosis assessment
- Efficacy: Muscle Biopsy: VCN: quantification of vector copy number per diploid cell
- Efficacy: Muscle Biopsy: SGCG transgene expression (at protein and mRNA levels)
- Efficacy: Muscle Biopsy: Quantification of human sarcolemmal SGCG-positive fibers by immunohistochemistry
- Efficacy: Muscle Biopsy: Quantification of human alpha-sarcoglycan positive fibers by immunohistochemistry
- Efficacy: Muscle Biopsy: Exploratory biomarkers, e.g., TMEM8 for regeneration, FN1 for fibrosis, and CD11b for inflammation, microRNA
- Efficacy: Patient reported outcome and QoL: Fatigue Visual Analog Scale (VAS)
- Efficacy: Patient reported outcome and QoL: EQ-5D-Y and EQ-5D-Y proxy 1 questionnaires (based on patient age)
- Efficacy: Patient reported outcome and QoL: Daily activity living (ACTIVLIM neuromuscular scale)
- Efficacy: Biomarkers: Creatine kinase (CK), myomesin-3, circulating microRNA
- Efficacy: Biomarkers: Blood and urine biobanking
研究者
Chief Medical officer
Scientific
Atamyo Therapeutics
研究点 (2)
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