2025-522603-15-00招募中2 期
A Phase IIb, Monocentric, Non-Profit, Open-label Trial for the Intrathecal Administration of AAV9/AP4M1 for Hereditary Spastic Paraplegia Type 50 (SPG50)
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii1 个研究点 分布在 1 个国家目标入组 5 人开始时间: 2026年2月6日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Change in total percent score of the eight Major Motor Milestones derived from the Gross Motor Function Measure (GMFM)-88 from baseline at W156.
研究概览
简要总结
To determine the efficacy of a single lumbar intrathecal administration of AAV9/AP4M1 on subjects affected by SPG50
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
- •Male or female subjects aged ≥ 6 years at the time of screening
- •Molecularly confirmed diagnosis of SPG50, defined as bi-allelic pathogenic variants in the AP4M1 gene, as determined by genomic DNA mutation analysis performed in a CLIA-certified, CE-marked, or equivalent laboratory.
- •Ability to sit independently for three seconds (corresponding to item 24 of the Gross Motor Function Measure GMFM-88).
- •Evidence of neurological dysfunction based on clinical history and physical examination.
- •Stable dosing of concomitant medications – including anti-spasticity medications, anti-epileptic medications, behavioral management medications, sleep medications, and special diets, supplements or nutritional support – for at least three months prior to screening. Subjects with recent changes in medications (<3 months) may be included at the Investigator’s discretion.
- •Availability of two legally competent custodial parents or legally acceptable representatives capable of providing informed consent as approved by the EC. In cases where only one parent has sole legal authority to consent, that parent must be able to actively participate in the consent process.
- •Legally acceptable representatives must be able to attend all scheduled study visits and provide feedback regarding the subject’s symptoms and performance as described in the protocol.
- •Subjects and caregivers must demonstrate ability to travel to the study center. For safety reasons, during the 30 days following treatment, subjects must domiciled at a location that allows them to reach the clinical site within approximately 90 minutes. As a practical reference, this corresponds to a maximum distance of about 150 km from the site.
- •Any sexually active male or female subject must be willing to use highly effective contraceptive methods for the full 5 years of the study and use a barrier method of contraception for 6 months post dosing, regardless of any other contraceptive method or sexual orientation.
排除标准
- •Inability to participate in the clinical evaluation, as determined by the Principal Investigators.
- •Any condition that would contraindicate MRI, per local institutional policy.
- •Any other condition that would preclude the subject from undergoing required study procedures.
- •Presence of significant AP-4-related CNS impairment or behavioral disturbances that would compromise the scientific rigor or interpretation of study results.
- •Laboratory abnormalities deemed potentially clinically significant.
- •Recent or planned elective surgical procedures that could confound the scientific rigor or interpretation of study results.
- •Failure to obtain valid informed consent.
- •Reason to believe that the subject or the parents of the subject will not comply with the procedures outlined in the study protocol.
- •Receipt of an investigational drug within 30 days prior to screening or plans to receive an investigational drug (other than gene therapy) during the study period.
- •Enrollment and participation in another interventional clinical trial 90 days before the first visit.
- •Clinically significant abnormal laboratory values (i.e., hemoglobin < 6 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; INR > ULN; GGT, ALT, and AST or total bilirubin > 1.5 × ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy.
- •Presence of a concomitant medical condition that precludes lumbar puncture or administration of anesthetic agents for procedures under deep sedation.
- •Bleeding disorders or any other medical condition or circumstance in which lumbar puncture is contraindicated, per local institutional policy.
- •Documented cardiomyopathy or significant congenital heart abnormalities.
- •Inability to undergo sedation safely, in the opinion of the clinical anesthesiologist.
- •History of severe or life-threatening allergic reactions to sirolimus, tacrolimus, corticosteroids, or gadolinium.
- •Concomitant illness or requirement for chronic drug treatment that, in the opinion of the Principal Investigator, poses undue risk during gene transfer.
- •Concomitant chronic drug treatment that would cause clinically significant interactions with study immunosuppressive agents.
结局指标
主要结局
Change in total percent score of the eight Major Motor Milestones derived from the Gross Motor Function Measure (GMFM)-88 from baseline at W156.
Change in total percent score of the eight Major Motor Milestones derived from the Gross Motor Function Measure (GMFM)-88 from baseline at W156.
次要结局
- Developmental Milestones (Vineland Adaptive Behavior Scale 3rd Edition [Vineland-3]) – Change in Total Score from Baseline.
- Developmental Milestones – Bayley Scale of Infant and Toddler Develop-ment 3rd Edition (Bayley-3) Cognitive Domain – Change in Total Raw Score from Baseline at W156.
- Gross and Fine Motor Function (GMFM-88 full scale) – Change in Total Score from Baseline at W156.
- Disease Severity (Spastic Paraplegia Rating Scale [SPRS]) – Change in Total Score from Baseline at W156.
- Disease Severity (Clinical Global Impression [CGI-I]) – Change in Physician-assessed CGI-I from Baseline at W156.
- Differential Ability Scales, 2nd Edition (DAS-II) - Change in Total Score from Baseline at W156.
- Developmental Milestones (Developmental Quotients [DQs]) – Change in DQs for Gross Motor, Adaptive behavior and Cognitive Scores from Base-line.
- Axonal Damage (Plasma neurofilament light chain levels [NfL]) – Change in Plasma NfL levels from Baseline.
- Health Related Quality of Life (The Caregiver Priorities and Child Health In-dex of Life with Disabilities [CPCHILD]) – Change in Total Score from Base-line.
- Disease Severity (Parent-rated Global Impression [PGI-I]) – Change in Glob-al Impression as assessed by the primary caregiver from Baseline.
- Axonal Damage (Cerebrospinal fluid [CSF] neurofilament light chain levels [NfL]) – Change in CSF NfL levels from Baseline.
- Serum and/or Plasma and CSF biomarkers – Change in Biomarker Levels from Baseline.
研究者
Lorenzo D’Antiga
Scientific
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
研究点 (1)
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