A Global, Multicenter, Single-arm, Matched External Control Study of Intrathecal SHP611 in Subjects with Late Infantile Metachromatic Leukodystrophy

Shire Human Genetic Therapies Inc.9 个研究点分布在 6 个国家目标入组 10 人开始时间: 2024年9月16日最近更新: 2024年11月8日

试验速览

阶段: 2 期
状态: 招募中
发起方: Shire Human Genetic Therapies Inc.
入组人数: 10
试验地点: 9
主要终点: 01. The primary efficacy endpoint is time to loss of locomotion, measured by progression to GMFC-MLD category 5 or higher, or death, whichever occurs first, up to Week 106, evaluated on subjects in Group A.

研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary objective of this study is to evaluate the effects of intrathecal (IT) administration of SHP611 on the time to loss of locomotion, as indicated by category 5 or higher in the Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with external control group data in children with late infantile MLD.

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）
接受健康志愿者: 否

入选标准

•The subject must have a documented diagnosis of MLD (Groups A-F) • Low ASA activity in leukocytes (compared to laboratory normal range) AND • Elevated sulfatides in urine
•The subject must have a gait disorder due to spastic ataxia or weakness attributable to MLD by the investigator and documented by a primary care physician or a specialist physician by 30 months of age (Groups A-C, and F), or be minimally symptomatic and ≥6 to <18 months of age (Group D); or be early symptomatic and ≥12 to <18 months of age (Group E). Subjects in Group E must have neurological symptoms documented by either a primary care physician or a specialist physician.
•The subject's age at the time of informed consent, must be: • Group A: 18 to 48 months of age • Group B: 18 to 72 months of age • Group C: 18 to 72 months of age • Group D: ≥6 to <18 months of age • Group E: ≥12 to <18 months of age • Group F: 18 to 72 months of age
•The subject's GMFC-MLD category at screening must be: • Group A: GMFC-MLD category of 1 or 2 • Group B: GMFC-MLD category of 3 • Group C: GMFC-MLD category of 4 • Group D: minimally symptomatic, and has the same ASA allelic constitution as an older sibling with confirmed late infantile or juvenile onset MLD • Group E: early symptomatic, ≥12 to <18 months of age with a GMFCMLD category of 1 or 2, and with a history of achieving stable walking (defined as at least 1 month of independent walking) • Group F: GMFC-MLD category of 5 or 6
•The subject and his/her parent/representative(s) must have the ability to comply with the clinical protocol.
•Subject's parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the subject.

排除标准

•Multiple sulfatase disorder as determined by abnormal activity of another lysosomal sulfatase (based upon the reference laboratory's normal range) or a known genetic disorder other than MLD
•The subject has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use a. The subject has had, or may have, an allergic reaction to the materials of construction b. The subject has shown an intolerance to an implanted device c. The subject's body size is too small to support the size of the SOPH-APORT Mini S Access Port d. The subject's drug therapy requires substances known to be incompatible with the materials of construction e. The subject has a known or suspected local or general infection f. The subject is at risk of abnormal bleeding due to a medical condition or therapy g. The subject has one or more spinal abnormalities that could complicate safe implantation or fixation h. The subject has a functioning CSF shunt device
•History of bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), or gene therapy or undergoes BMT, HSCT, or gene therapy at any point during the study
•Primary presentation of MLD was behavioral or cognitive symptoms (per investigator's clinical judgment); behavioral symptoms that are secondary to motor deficits (eg: tantrums in response to loss of motor skills) are not exclusionary.
•The subject has any known or suspected hypersensitivity to agents used for anesthesia or has history of difficult airway or potential for airway compromise
•Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study
•Subjects with laboratory, ECG, or vital sign abnormalities reflecting intercurrent illness that may compromise their safety during the trial should not be enrolled. Abnormal laboratory, vital sign and ECG results at screening should be reviewed with the Takeda medical monitor.
•The subject is enrolled in another clinical study that involves use of any investigational product (drug or device) within 30 days or 5 halflives (whichever is longer) prior to study enrollment or at any time during the study
•The subject has had prior exposure to SHP611
•The subject must weight > 11lbs (5kg)

结局指标

主要结局

01. The primary efficacy endpoint is time to loss of locomotion, measured by progression to GMFC-MLD category 5 or higher, or death, whichever occurs first, up to Week 106, evaluated on subjects in Group A.

次要结局

01. Response in Group A, defined as maintenance of gross motor function at Week 106, evaluated as subjects who do not experience any event within Week 106, where event is defined as a decline in GMFC MLD to category 5 or higher, or death
02. Decline in gross motor function using GMFC MLD: - Change from baseline at Week 106 and EOS in gross motor function, using the GMFC MLD - Subjects with unreversed decline from baseline in GMFC-MLD of more than 2 categories, defined as any decline of more than 2-categories that has not reverted to a 2-category decline (or better) at Week 106, evaluated on subjects in Group A
02. Decline in gross motor function using GMFC MLD: - Time to unreversed decline from baseline in GMFC-MLD of more than 2 categories, defined as any decline of more than 2-categories that has not reverted to a 2-category decline (or better) as of the last recorded observation
03. Change from baseline at Week 106 and EOS in CSF sulfatides levels
04. Response in Group A, defined as maintenance of gross motor function at Week 106, defined as a GMFM 88 total score ≥40
05. Decline in gross motor function using GMFM-88: - Time to unreversed decline from baseline at Week 106 and EOS in GMFM-88 total score decrease of >20 points or unreversed decline to a score <40 points, whichever occurs first
05. Decline in gross motor function using GMFM-88: - Change from baseline at Week 106 and EOS in gross motor function, using the GMFM-88 total score - Subjects in Group A with GMFM-88 total score decrease of ≤20 points from baseline and a total score that is ≥40 at Week 106 and EOS
06. Change from baseline at Week 106 and EOS in expressive language using the ELFC-MLD

研究者

发起方

Shire Human Genetic Therapies Inc.

申办方类型

Pharmaceutical company

责任方

Principal Investigator

主要研究者

CJ Malanga

Scientific

Shire Human Genetic Therapies Inc.

研究点 (9)

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