Tralesinidase alfa(Tralesinidase alfa) - 药物靶点：HS_在研适应症：黏多醣贮积症III型_专利_临床

概要

基本信息

药物类型

融合蛋白

别名

NAGLU-IGF2 fusion protein

+ [1]

靶点

HS

作用机制

硫酸乙酰肝素硫酸酯酶替代物

治疗领域

遗传病与畸形内分泌与代谢疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

黏多醣贮积症III型

非在研适应症-

原研机构

BioMarin Pharmaceutical, Inc.

在研机构

Allievex Corp.

非在研机构

BioMarin Pharmaceutical, Inc.

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)无进展

特殊审评-

序列信息

Sequence Code 318417585

来源: *****

关联

5

项与 Tralesinidase alfa 相关的临床试验

EUCTR2017-003083-13-GB / Unknown status临床2期

A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Safety and Efficacy of Intracerebroventricular AX 250 in Patients with Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

开始日期2018-03-02

申办/合作机构

Allievex Corp.

NCT03784287 / Active, not recruiting临床2期

A Multicenter, Multinational, Extension Study to Evaluate the Long Term Safety and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

The primary objectives of this study are to evaluate the long-term safety and tolerability of AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and to evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).

开始日期2018-02-19

申办/合作机构

Allievex Corp.

NCT02754076 / Completed临床1/2期

A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

The study's primary objectives are to evaluate the safety and tolerability of AX 250 administered to subjects with MPS IIIB via an ICV reservoir and catheter and to evaluate the impact of AX 250 on cognitive function in patients with MPS IIIB as assessed by the Development Quotient.

开始日期2016-04-01

申办/合作机构

Allievex Corp.

100 项与 Tralesinidase alfa 相关的临床结果

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100 项与 Tralesinidase alfa 相关的转化医学

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100 项与 Tralesinidase alfa 相关的专利（医药）

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9

项与 Tralesinidase alfa 相关的文献（医药）

2023-09-12·International journal of molecular sciences

Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice.

Article

作者: Aguirre, Jose I ; Sommerville, John D ; Chen, Cong ; Ashby, Frederick James ; Jamieson, Julia C ; Andraka, Natalia K ; Castillo, Evelyn J ; Kabbej, Nadia ; Heldermon, Coy D ; Ludwig, Yan

Sanfilippo syndrome Type-B, also known as mucopolysaccharidosis IIIB (MPS IIIB), accounts for approximately one-third of all Sanfilippo syndrome patients and is characterized by a similar natural history as Type-A. Patients suffer from developmental regression, bone malformation, organomegaly, GI distress, and profound neurological deficits. Despite human trials of enzyme replacement therapy (ERT) (SBC-103, AX250) in MPS IIIB, there is currently no FDA approved treatment and a few palliative options. The major concerns of ERT and gene therapy for the treatment of bone malformation are the inadequate biodistribution of the missing enzyme, N-acetyl-α-glucosaminidase (NAGLU), and that the skeleton is a poorly hit target tissue in ERT and gene therapy. Each of the four known human types of MPS III (A, B, C, and D) is usually regarded as having mild bone manifestations, yet it remains poorly characterized. This study aimed to determine bone mineral content (BMC), volumetric bone mineral density (vBMD), and biomechanical properties in femurs MPS IIIB C57BL/6 mice compared to phenotypic control C57BL/6 mice. Significant differences were observed in MPS IIIB mice within various cortical and cancellous bone parameters for both males and females (p < 0.05). Here, we establish some osteogenic manifestations of MPS IIIB within the mouse model by radiographic and biomechanical tests, which are also differentially affected by age and sex. This suggests that some skeletal features of the MPS IIIB mouse model may be used as biomarkers of peripheral disease correction for preclinical treatment of MPS IIIB.

2023-01-17·Journal of Clinical Investigation

A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B

Article

作者: von Cossel, Katharina ; Harmatz, Paul ; Batzios, Spyros ; Couce, Maria Luz ; de Castro Lopez, Maria J ; Kovalchin, Joseph ; Cleary, Maureen ; Maricich, Stephen M ; Solano, Martha ; Zanelli, Eric ; Lin, Shuan-Pei ; Koehn, Anja ; Kuca, Bernice ; Shaywitz, Adam J ; Okur, Ilyas ; Kaufman, Brian ; Nestrasil, Igor ; Ezgu, Fatih ; Muschol, Nicole

BackgroundSanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline.MethodsIn this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores.ResultsIn the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV.ConclusionAdministration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy.Trial registrationClinicaltrials.gov NCT02754076.FUNDINGBioMarin Pharmaceutical Inc. and Allievex Corporation.

2023-01-01·Toxicology Reports

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys

Article

作者: Chandra, Sundeep ; Grover, Anita ; Henshaw, Joshua ; Trombley, Jami L. ; Zanelli, Eric ; Nguyen, Annalisa ; Pinkstaff, Jason ; Melton, Andrew C. ; Boyd, Robert B. ; Butt, Mark T. ; Adams, Eric. L. ; Kovalchin, Joseph ; Reed, Randall P. ; Cherukuri, Anu ; McCullagh, Emma ; O′Neill, Charles A. ; Wait, Jill CM

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB. Since MPS IIIB is a pediatric disease the safety/toxicity, pharmacokinetics and biodistribution of TA were evaluated in juvenile non-human primates that were administered up to 5 weekly intracerebroventricular (ICV) or single intravenous (IV) infusions of TA. TA administered by ICV slow-, ICV isovolumetric bolus- or IV-infusion was well-tolerated, and no effects were observed on clinical observations, electrocardiographic or ophthalmologic parameters, or respiratory rates. The drug-related changes observed were limited to increased cell infiltrates in the CSF and along the ICV catheter track after ICV administration. These findings were not associated with functional changes and are associated with the use of ICV catheters. The CSF PK profiles were consistent across all conditions tested and TA distributed widely in the CNS after ICV administration. Anti-drug antibodies were observed but did not appear to significantly affect the exposure to TA. Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB.

100 项与 Tralesinidase alfa 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
黏多醣贮积症III型	临床3期	德国	Allievex Corp.	2022-10-18
黏多醣贮积症III型	临床3期	土耳其	Allievex Corp.	2022-10-18
黏多醣贮积症III型	临床3期	英国	Allievex Corp.	2022-10-18
黏多醣贮积症III型	临床3期	美国	Allievex Corp.	2022-10-18
黏多醣贮积症III型	临床3期	哥伦比亚	Allievex Corp.	2022-10-18

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02754076 (Pubmed) 人工标引	临床1/2期	黏多醣贮积症III型	22	Tralesinidase alfa	(淵築繭膚構繭襯網鏇憲) = Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. 鏇鏇選構蓋顧範齋窪繭 (顧鬱簾繭壓簾鹽蓋鬱築 ) 更多	积极	2022-11-22