Open-Label Early Access Treatment With Intracerebroventricular Tralesinidase Alfa in Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)
试验速览
- 阶段
- 不适用
- 状态
- Available
研究概览
简要总结
This is an intermediate-size patient population Early Access Program (EAP) providing access to intracerebroventricular (ICV) tralesinidase alfa (TA) for participants with mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo Syndrome Type B). The primary objectives are to allow early access to TA treatment and to evaluate the safety and tolerability of TA ICV infusion. Approximately 10 participants will be enrolled at up to 3 US sites and treated with TA once weekly via ICV infusion for up to approximately 52 weeks, or until TA becomes commercially available.
详细描述
MPS IIIB (Sanfilippo Syndrome Type B) is an ultra-rare, autosomal recessive lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU). In the absence of NAGLU activity, heparan sulfate (HS) and its metabolite HS non-reducing end (HS-NRE) accumulate in lysosomes, causing progressive CNS neurodegeneration. Affected children experience developmental delays beginning between ages 1 and 4, followed by cognitive regression and loss of motor function, with death typically occurring in the second decade of life.
Tralesinidase alfa (TA) is a recombinant human NAGLU-IGF2 fusion protein administered directly into the CNS via ICV infusion. In Study 250-201 and its extension studies, weekly ICV TA normalized or near-normalized CSF HS-NRE levels in all participants within 4 weeks, with effects maintained for up to 5 years. TA treatment was associated with long-term stabilization of cortical gray matter volume and prevention of age-dependent cognitive decline.
Study 250-502 is an intermediate-size EAP under 21 CFR 312.315, intended for participants who are older than 5 years of age or have a BSID-III-C raw score ≥70. The program will continue until TA receives US regulatory approval and commercial availability, or until the allocated TA supply is exhausted.
Participants receive TA (200 mg if age 1 to <2 years; 300 mg if age ≥2 years) administered via ICV infusion once weekly after surgical implantation of an ICV access device (reservoir and catheter). The first ICV infusion is administered in an inpatient setting; subsequent infusions are done in an outpatient setting. Participants are pretreated with antihistamine approximately 30 minutes before each infusion.
研究设计
- 研究类型
- Expanded Access
入排标准
- 年龄范围
- 12 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a diagnosis of MPS IIIB confirmed by deficient NAGLU enzyme activity analyzed at the laboratory during Screening.
- •Is ≥12 and ≤60 months of age with a BSID-III-C raw score ≥
- •or Is >60 months of age regardless of cognitive level. Has provided written informed consent from a parent or legal guardian Has been determined by the investigator, after consultation with the participant (if applicable) and their family/caregiver, that the known risks of TA ICV infusion are outweighed by its potential benefits.
- •If female and of childbearing potential, agrees to follow contraception guidelines from screening until 30 days after the last dose of TA.
- •Has the ability to comply with program requirements, in the opinion of the investigator.
排除标准
- •Has contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities).
- •Has contraindications for MRI scans, if the investigator deems an MRI and not a CT scan is required for ICV access device placement or follow-up post-placement.
- •Has a history of poorly controlled seizure disorder. Is prone to complications from ICV infusion, including participants with hydrocephalus or ventricular shunts.
- •Has received any investigational medication within 30 days prior to the Baseline Visit or is scheduled to receive any investigational drug during the course of the program.
- •Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the participant's ability to comply with program requirements, the participant's well-being or safety, or the interpretability of the participant's clinical data.