Modified recombinant human sulphamidase(Swedish Orphan Biovitrum)(Modified recombinant human sulphamidase(Swedish Orphan Biovitrum))

概要

基本信息

药物类型

酶

别名

Recombinant-sulfamidase-Swedish-Orphan-Biovitrum

靶点-

作用方式-

作用机制-

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-

非在研适应症

黏多醣贮积症III型

原研机构

Swedish Orphan Biovitrum AB

在研机构-

非在研机构

Swedish Orphan Biovitrum AB

权益机构-

最高研发阶段无进展临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评快速通道 (美国)

登录后查看时间轴

结构/序列

Sequence Code 123346

来源: *****

关联

2

项与 Modified recombinant human sulphamidase(Swedish Orphan Biovitrum) 相关的临床试验

NCT03811028

/ Completed临床1/2期

An Open, Single-arm, Multicenter Extension Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients

MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS IIIA is characterized by devastating neurodegeneration with initially mild somatic involvement. The aim of the present study is to assess the safety, tolerability and efficacy of long-term SOBI003 treatment. SOBI003 is a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).

开始日期2019-01-19

申办/合作机构

Swedish Orphan Biovitrum AB

NCT03423186

/ Completed临床1/2期

An Open, Non-controlled, Parallel, Ascending Multiple-dose, Multicenter Study to Assess Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of SOBI003 in Pediatric MPS IIIA Patients

MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS IIIA is characterized by devastating neurodegeneration with initially mild somatic involvement. The aims of the present study is to assess the dose related safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SOBI003, a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).

开始日期2018-06-19

申办/合作机构

Swedish Orphan Biovitrum AB

100 项与 Modified recombinant human sulphamidase(Swedish Orphan Biovitrum) 相关的临床结果

登录后查看更多信息

100 项与 Modified recombinant human sulphamidase(Swedish Orphan Biovitrum) 相关的转化医学

登录后查看更多信息

100 项与 Modified recombinant human sulphamidase(Swedish Orphan Biovitrum) 相关的专利（医药）

登录后查看更多信息

5

项与 Modified recombinant human sulphamidase(Swedish Orphan Biovitrum) 相关的文献（医药）

2022-08-01·Molecular Genetics and Metabolism

Chemically modified recombinant human sulfamidase (SOBI003) in mucopolysaccharidosis IIIA patients: Results from an open, non-controlled, multicenter study

Article

作者: Huledal, Gunilla ; Bröijersén, Anders ; Harmatz, Paul ; Dalén, Per ; Wikén, Margareta ; Ezgü, Fatih ; Önnestam, Kristin ; Gelius, Stefan Svensson ; Lindqvist, Daniel ; Muenzer, Joseph

PURPOSEMucopolysaccharidosis IIIA (MPS IIIA) is an inherited lysosomal storage disorder caused by mutations in the N-sulfoglucosamine sulfohydrolase gene that result in deficient enzymatic degradation of heparan sulfate (HS), resulting in progressive neurodegeneration in early childhood and premature death. A chemically modified variant of recombinant human sulfamidase, SOBI003, has shown to cross the blood-brain barrier (BBB) in mice and achieve pharmacologically relevant levels in cerebrospinal fluid (CSF). We report on a phase 1/2, open-label, first-in-human (FIH) study (NCT03423186) and its extension study (NCT03811028) to evaluate the long-term safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD) and clinical efficacy of SOBI003 in patients with MPS IIIA for up to 104 weeks.METHODSSix patients aged 1-6 years with confirmed MPS IIIA with developmental age ≥ 12 months received weekly intravenous injections of SOBI003 at 3 mg/kg (Cohort 1, n = 3) or 10 mg/kg (Cohort 2, n = 3). During the extension study, the individual dose of SOBI003 could be adjusted up to 20 mg/kg at the discretion of the investigator.RESULTSSOBI003 was generally well tolerated. Serum concentrations of SOBI003 increased in proportion to dose, and presence in CSF confirmed that SOBI003 crosses the BBB. Anti-drug antibodies (ADA) were detected in serum and CSF in all patients, with subsequent reductions in serum SOBI003 exposure at high ADA titers. SOBI003 exerted a clear PD effect: a mean reduction in HS levels in CSF of 79% was recorded at the last assessment, together with reductions in HS levels in serum and urine. Neurocognitive development age-equivalent scores showed a stabilization of cognition for all patients, whereas no clear overall clinical effect was observed on adaptive behavior, sleep pattern or quality of life.CONCLUSIONSOBI003 was well tolerated when administered as weekly intravenous infusions at doses of up to 20 mg/kg for up to 104 weeks. ADA development was common and likely affected both PK and PD parameters. SOBI003 crossed the BBB and showed pharmacological activity on HS in CSF.

2017-05-01·Journal of Inherited Metabolic Disease2区 · 医学

Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric‐onset neurodegenerative disease, MPS IIIA

2区 · 医学

Article

作者: Hopwood, John J ; Marshall, Neil R ; Hassiotis, Sofia ; Jolly, Robert D ; King, Barbara ; Tucker, Justin ; Hattersley, Kathryn ; Trim, Paul J ; Hemsley, Kim M ; Snel, Marten F

AbstractIntra‐cerebrospinal fluid (CSF) injection of recombinant human lysosomal enzyme is a potential treatment strategy for several neurodegenerative lysosomal storage disorders including Sanfilippo syndrome (Mucopolysaccharidosis type IIIA; MPS IIIA). Here we have utilised the MPS IIIA Huntaway dog model to compare the effectiveness of the repeated intermittent bolus injection strategy being used in the trials with an alternate approach; slow, continual infusion of replacement enzyme (recombinant human sulphamidase; rhSGSH) into the spinal CSF using a SynchroMed II® pump attached to a spinal infusion cannula. The ability of each enzyme delivery strategy to ameliorate lesions in MPS IIIA brain was determined in animals treated from ∼three‐ to six‐months of age. Controls received buffer or no treatment. Significant reductions in heparan sulphate (primary substrate) were observed in brain samples from dogs treated via either cisternal or lumbar spinal CSF bolus injection methods and also in slow intra‐spinal CSF infusion‐treated dogs. The extent of the reduction differed regionally. Pump‐delivered rhSGSH was less effective in reducing secondary substrate (GM3 ganglioside) in deeper aspects of cerebral cortex, and although near‐amelioration of microglial activation was seen in superficial (but not deep) layers of cerebral cortex in both bolus enzyme‐treated groups, pump‐infusion of rhSGSH had little impact on microgliosis. While continual low‐dose infusion of rhSGSH into MPS IIIA dog CSF reduces disease‐based lesions in brain, it was not as efficacious as repeated cisternal or spinal CSF bolus infusion of rhSGSH over the time‐frame of these experiments.

2016-05-01·Journal of Neurochemistry2区 · 医学

Low‐dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA

2区 · 医学

Article

作者: Snel, Marten F. ; Hassiotis, Sofia ; Beard, Helen ; Hopwood, John J. ; King, Barbara ; Trim, Paul J. ; Hemsley, Kim M. ; Rozaklis, Tina

AbstractRepeated replacement of sulphamidase via cerebrospinal fluid injection is an effective treatment for pathological changes in the brain in mice and dogs with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). Investigational trials of this approach are underway in children with this condition, however, infusions require attendance at a specialist medical facility. We sought to comprehensively evaluate the effectiveness of sustained‐release (osmotic pump‐delivered) enzyme replacement therapy in murine MPS IIIA as this method, if applied to humans, would require only subcutaneous administration of enzyme once the pump was installed. Six‐week‐old MPS IIIA and unaffected mice were implanted with subcutaneous mini‐osmotic pumps connected to an infusion cannula directed at the right lateral ventricle. Either recombinant human sulphamidase or vehicle were infused over the course of 7 weeks, with pumps replaced part‐way through the experimental period. We observed near‐normalisation of primarily stored substrate (heparan sulphate) in both hemispheres of the MPS IIIA brain and cervical spinal cord, as determined using tandem mass spectrometry. Immunohistochemistry indicated a reduction in secondarily stored GM3 ganglioside and neuroinflammatory markers. A bias towards the infusion side was seen in some, but not all outcomes. The recombinant enzyme appears stable under pump‐like conditions for at least 1 month. Given that infusion pumps are in clinical use in other nervous system disorders, e.g. for treatment of spasticity or brain tumours, this treatment method warrants consideration for testing in large animal models of MPS IIIA and other lysosomal storage disorders that affect the brain.

image

Clinical trials of repeated injection of replacement enzyme into CSF are underway in patients with the inherited neurodegenerative disorder mucopolysaccharidosis type IIIA. In this pre‐clinical study, we examined an alternative approach – slow, continual infusion of enzyme using pumps. We observed significant reductions in substrate accumulation and other disease‐based lesions in treated mouse brain. Thus, the strategy warrants consideration for testing in large animal models of MPS IIIA and also in other neurodegenerative lysosomal storage disorders.

100 项与 Modified recombinant human sulphamidase(Swedish Orphan Biovitrum) 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15451

研发状态

10 条进展最快的记录,

登录

后查看更多信息

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2期	美国	Swedish Orphan Biovitrum AB	2018-06-19
黏多醣贮积症III型	临床2期	德国	Swedish Orphan Biovitrum AB	2018-06-19
黏多醣贮积症III型	临床2期	土耳其	Swedish Orphan Biovitrum AB	2018-06-19

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03423186 \| NCT03811028 (SOBI003, Pubmed) 人工标引	临床1/2期	黏多醣贮积症III型	6	SOBI003	淵鹽鹽顧鹽顧餘獵顧餘(鹹艱廠網鏇憲製淵製願) = 遞繭壓膚鑰蓋鹽繭蓋糧範遞餘壓鏇構遞糧夢鏇 (醖窪獵醖憲製鹽構簾製 )	积极	2022-06-28
NCT03811028 (CTgov)	临床1/2期	黏多醣贮积症III型	6	SOBI003 (Dose Group 1)	(顧壓選繭夢構艱繭膚蓋) = 窪蓋蓋製衊窪鹹選鹽壓觸廠夢觸構夢蓋構網衊 (積鬱構鬱鑰衊餘膚構鹹, 遞顧構鬱製觸醖憲範鏇 ~ 簾窪製鑰憲衊襯鑰遞積) 更多	-	2022-02-25
				SOBI003 (Dose Group 2)	(顧壓選繭夢構艱繭膚蓋) = 夢淵顧蓋醖製膚選衊淵觸廠夢觸構夢蓋構網衊 (積鬱構鬱鑰衊餘膚構鹹, 憲壓觸齋糧構選衊製積 ~ 襯鬱齋餘艱艱顧壓餘醖) 更多
NCT03423186 (CTgov)	临床1/2期	黏多醣贮积症III型	6	SOBI003 (Dose Group 1)	(蓋鏇淵醖鹽願窪襯鏇鹽) = 鑰艱襯襯顧鑰網網製醖窪製顧鹹築構鏇襯餘鹹 (艱膚積窪選憲窪壓鏇鹽, 齋艱遞積網壓觸壓窪構 ~ 鏇淵構鹽窪構網鑰淵憲) 更多	-	2021-04-22
				SOBI003 (Dose Group 2)	(蓋鏇淵醖鹽願窪襯鏇鹽) = 襯製願構膚艱鏇淵窪糧窪製顧鹹築構鏇襯餘鹹 (艱膚積窪選憲窪壓鏇鹽, 鏇願壓壓繭觸糧選鑰蓋 ~ 艱鏇鏇製築範廠積鬱繭) 更多