NCT06692712招募中3 期
Intrathecal Administration of MELPIDA (AAV9/AP4M1) For Hereditary Spastic Paraplegia Type 50 (SPG50): A Phase 3, Open-Label Trial With Matched Prospective Concurrent Control Arm
Elpida Therapeutics SPC2 个研究点 分布在 2 个国家目标入组 24 人开始时间: 2026年4月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Gross Motor Function Measure (GMFM-88) Defined Major Milestones
研究概览
简要总结
Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50).
详细描述
MELPIDA is an AAV9-based gene therapy vector that expresses the fully functional form of AP4M1 under the control of a synthetic promoter. MELPIDA will be delivered intrathecally and is designed to achieve stable, potentially life-long expression of AP4M1 in non-dividing cells. This clinical study is a pivotal open-label phase 3 study designed to assess safety and efficacy of MELPIDA in individuals with SPG50.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Months 至 72 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For the treatment group
- •Male and females between the ages of 4 months to 72 months at the time of screening.
- •Molecularly-confirmed diagnosis of SPG50 (confirmed by a CLIA certified, CE-marked, or equivalent lab): Genomic DNA mutation analysis demonstrating bi-allelic pathogenic or likely pathogenic variants in the AP4M1 gene.
- •Subjects must have features of neurologic dysfunction by clinical history and physical examination.
- •Stable doses of concomitant medications such as anti-spasticity medications, anti-seizure medications, behavioral management medications, sleep medications, and special diets, supplements, or nutritional support for at least 3 months prior to Screening. If recent changes (< 3 months) in medications, the subject may be allowed per Investigator judgement.
- •Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study,
- •Subjects and caregivers must demonstrate the ability to travel to the study center. For the 30 days post treatment subjects must reside within 100 miles (approximately 160 km) of the clinical site.
- •For the control group
- •Male and females between the ages of 4 to 72 months at the time of screening.
- •A molecularly confirmed diagnosis of SPG47, SPG50 or SPG52 (confirmed by a CLIA certified, CE-marked, or equivalent lab). Genomic DNA mutation analysis demonstrating bi-allelic pathogenic variants in the AP4B1, AP4M1, or AP4S1 gene,
- •Subjects must have features of neurologic dysfunction by clinical history and physical examination.
- •Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study.
- •Subject able to comply with all protocol requirements and procedures.
- •Subjects and caregivers must demonstrate the ability to travel to the study center.
- •For the treatment group
- •Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
- •#24: Sit on mat: Maintain, arms free, 3 seconds
- •#44: 4 Point: Crawls or hitches forward 1.8m (6')
- •#53: Standing: Maintains, arms free, 3 seconds
- •#67: Standing: 2 hands held: walks forward 10 steps
- •#69: Standing: Walks forward 10 steps
- •#84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
- •#85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
- •#88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
- •Inability to participate in the clinical evaluation as determined by the principal investigators.
- •Clinically significant abnormal laboratory values (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 (eg, scoliosis or bleeding disorder) that precludes a lumbar puncture or use of anesthetics for sedated procedures.
- •Documented cardiomyopathy or significant congenital heart abnormalities.
- •History of severe/life-threatening allergic reaction to sirolimus, tacrolimus, corticosteroids, or gadolinium.
- •Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or interactions with the immunosuppressive agents.
- •Any item which would exclude the subject from being able to undergo MRI according to local institutional policy, or any other procedure.
- •The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- •Recent or planned elective surgical procedures (within 6 months) that would confound the scientific rigor or interpretation of results of the study.
- •Failure to obtain appropriate informed consent.
- •Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
- •Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
- •Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).
- •For the control group
- •Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:
- •#24: Sit on mat: Maintain, arms free, 3 seconds
- •#44: 4 Point: Crawls or hitches forward 1.8m (6')
- •#53: Standing: Maintains, arms free, 3 seconds
- •#67: Standing: 2 hands held: walks forward 10 steps
- •#69: Standing: Walks forward 10 steps
- •#84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet
- •#85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet
- •#88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
- •Inability to participate in the clinical evaluation as determined by the principal investigators.
- •Any other situation that would exclude the subject from undergoing any other procedure required in this study.
- •The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- 另有 5 项未显示
排除标准
- •For the treatment group
- •Inability to participate in the clinical evaluation as determined by the principal investigators.
- •Clinically significant abnormal laboratory values (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 (eg, scoliosis or bleeding disorder) that precludes a lumbar puncture or use of anesthetics for sedated procedures.
- •Documented cardiomyopathy or significant congenital heart abnormalities.
- •History of severe/life-threatening allergic reaction to sirolimus, tacrolimus, corticosteroids, or gadolinium.
- •Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or interactions with the immunosuppressive agents.
- •Any item which would exclude the subject from being able to undergo MRI according to local institutional policy, or any other procedure.
- •The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- •Recent or planned elective surgical procedures (within 6 months) that would confound the scientific rigor or interpretation of results of the study.
- •Failure to obtain appropriate informed consent.
- •Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
- •Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
- •Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).
- •For the control group
- •Inability to participate in the clinical evaluation as determined by the principal investigators.
- •Any other situation that would exclude the subject from undergoing any other procedure required in this study.
- •The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- •Recent or planned elective surgical procedures that would confound the scientific rigor or interpretation of results of the study.
- •Failure to obtain appropriate informed consent.
- •Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
- •Have received an investigational drug within 30 days prior to screening or plans to receive an investigational drug (other than gene therapy) during the study.
- •Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).
研究组 & 干预措施
Matched Prospective Concurrent Control Arm
No Intervention
Approximately 16 untreated age- and disease- matched controls with confirmed AP-4-related disease (SPG47, SPG50, or SPG52) will be enrolled and attend study visits concurrent with the MELPIDA treatment arm.
MELPIDA Treatment
Experimental
Eligible subjects (N=8) will receive a single open-label intrathecal administration of MELPIDA and follow up to week 260.
干预措施: MELPIDA (Genetic)
结局指标
主要结局
Gross Motor Function Measure (GMFM-88) Defined Major Milestones
时间窗: 156 weeks
Change in total percent score of the 8 Major Motor Milestone Scores from baseline in treated group compared to change in total percent score of the 8 Major Motor Milestone Scores from baseline in untreated controls 1. #24: Sit on mat: Maintain, arms free, 3 seconds 2. #38: Prone: Creeps forward 1.8m (6') 3. #52: On the floor: Pulls to stand at large bench 4. #67: Standing: 2 hands held: walks forward 10 steps 5. #69: Standing: Walks forward 10 steps 6. #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet 7. #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet 8. #88: Standing on 15cm (6") step: Jumps off, both feet simultaneously
次要结局
- Disease Severity (Spastic Paraplegia Rating Scale [SPRS])(156 weeks)
- Muscle Spasticity (Modified Ashworth Scale [MAS])(156 weeks)
- Composite Endpoint Defined by the Win Ratio(156 weeks)
- Developmental Milestones- Bayley-4 Cognitive Domain(156 weeks)
- Gross and Fine Motor Function (GMFM-88 full scale)(156 weeks)
- Disease Severity (Clinical Global Impression [CGI-I])(156 weeks)
- Disease Severity (Spastic Paraplegia Rating Scale )(156 weeks)
- Disease Severity (Clinical Global Impression)(156 weeks)
- Muscle Spasticity (Modified Ashworth Scale)(156 weeks)
研究者
研究点 (2)
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