(SHP-610) - 药物靶点：HS_专利_临床

概要

基本信息

药物类型

酶

别名

Recombinant human heparan N-sulfatase、rhHNS

+ [2]

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-

非在研适应症

黏多醣贮积症III型

原研机构

Shire Plc

在研机构-

非在研机构

Shire Plc

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

关联

4

项与 SHP-610 相关的临床试验

NCT02350816 / Terminated临床2期

An Open-Label Extension of Study HGT-SAN-093 Evaluating the Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Mucopolysaccharidosis Type IIIA Disease

This extension study will allow participants to continue receiving treatment with HGT-1410 and to initiate treatment in patients who received no-treatment in Study HGT-SAN-093, and will evaluate the long-term safety and efficacy of the study drug.

开始日期2015-04-08

申办/合作机构

Shire Plc

EUCTR2013-003450-24-IT / Not yet recruiting临床2期

A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration via an Intrathecal Drug Delivery Device in Pediatric Patients with Early Stage Mucopolysaccharidosis Type III A Disease

开始日期2014-09-11

申办/合作机构

Shire Human Genetic Therapies, Inc.

NCT02060526 / Completed临床2期

A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of rhHNS (Recombinant Human Heparan N Sulfatase) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Early Stage Mucopolysaccharidosis Type IIIA Disease

Sanfilippo syndrome Type A, or Mucopolysaccharidosis (MPS) IIIA, is a rare lysosomal storage disease caused by deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, there is an accumulation of the glycosaminoglycan, heparan sulfate, resulting in progressive neurodegeneration. Symptoms are usually first noted in the 1st or 2nd year of life, although definitive diagnosis is often delayed, with an average age of diagnosis of 4.5 years. The disease is characterized by developmental delays initially, followed by neurological developmental arrest, then regression. These developmental deficits are typically associated with severe behavioral disturbances. Patients have a significantly reduced lifespan, with few surviving beyond the 2nd or 3rd decade.
The purpose of this study is to evaluate the safety and efficacy of recombinant human heparan-N-sulfatase (rhHNS) in pediatric patients with Early Stage Mucopolysaccharidosis Type III A Disease.

开始日期2014-02-26

申办/合作机构

Shire Plc

100 项与 SHP-610 相关的临床结果

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100 项与 SHP-610 相关的转化医学

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100 项与 SHP-610 相关的专利（医药）

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6

项与 SHP-610 相关的文献（医药）

2021-12-01·Molecular Genetics and Metabolism2区 · 生物学

Long-term safety and clinical outcomes of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A

2区 · 生物学

Article

作者: de Ruijter, Jessica ; Alexanderian, David ; Rust, Stewart ; Wijburg, Frits A ; Heap, Fiona ; Tump, Evelien ; Nestrasil, Igor ; Jones, Simon A ; Marchal, Jan Pieter ; Shapiro, Elsa

INTRODUCTIONCurrently, there is no effective therapy for mucopolysaccharidosis IIIA (MPS IIIA). Intravenously-administered enzyme replacement therapies, while effective in other forms of MPS without neurological involvement, have not been successful in patients with MPS IIIA, as they are unable to cross the blood-brain barrier to improve neurological symptoms. We evaluated the long-term safety, tolerability, and clinical outcomes of recombinant human heparan-N-sulfatase (rhHNS) administered intrathecally (IT) in children with MPS IIIA in a phase 1/2 extension study.METHODSPatients aged ≥3 years with MPS IIIA who had previously completed a phase 1/2 study and received ≥5 of the 6 planned rhHNS infusions via IT administration, were eligible for inclusion. Patients who received 10 mg in the phase 1/2 study had their dose increased to 45 mg. Patients who were treated with 45 mg or 90 mg rhHNS IT in the phase 1/2 study remained on this monthly dose in the extension study. rhHNS was administered via an intrathecal drug delivery device (IDDD). Primary endpoints included the type and severity of adverse events, presence of anti-rhHNS antibodies in the CSF and serum, and changes in laboratory values. Secondary endpoints included standardized neurocognitive assessments and brain magnetic resonance imaging.RESULTSIn the extension study, 12 patients with a mean (SD) age of 9.6 (7.3) years continued treatment with rhHNS IT for a median of 264.4 weeks. Ten of 12 patients completed the extension study. rhHNS IT was generally well-tolerated. All patients experienced at least one treatment-emergent adverse event (TEAE), most being mild or moderate in severity. No serious adverse events (SAEs) were considered related to the study drug, and no deaths occurred. Most SAEs were related to malfunctions of the IDDD. Declines from baseline in Bayley Scales of Infant Development, Third Edition or Kaufman Assessment Battery for Children, Second Edition, Nonverbal Index developmental quotient scores were evident at all rhHNS dosing groups: -17.97%, -18.99%, and -12.12% in the 10/45, 45, and 90 mg groups, respectively, at Month 54.CONCLUSIONSOverall, rhHNS IT was well tolerated in the extension study. However, rhHNS IT was unable to slow the neurocognitive decline of patients with MPS IIIA. This study was subsequently terminated early because pre-specified efficacy criteria were not met, and the study did not yield clinical proof of concept. (Clinicaltrials.gov Identifier NCT01299727).

2021-09-01·Molecular Genetics and Metabolism2区 · 生物学

A multicenter open-label extension study of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A

2区 · 生物学

Article

作者: Gasperini, Serena ; Shapiro, Elsa ; Wijburg, Frits A ; Alexanderian, David ; Del Toro, Mireia ; Muschol, Nicole ; Whitley, Chester B ; Muenzer, Joseph ; Cleary, Maureen ; Sevin, Caroline

Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a rare autosomal recessive lysosomal disorder characterized by deficient heparan-N-sulfatase (HNS) activity, and subsequent accumulation of heparan sulfate, especially in the central nervous system. The disease is associated with progressive neurodegeneration in early childhood. For this open-label extension study of a phase 2b clinical trial, we report on safety and cognitive decline in patients receiving intrathecal (IT) administration of recombinant human HNS (rhHNS). Of 21 patients who completed the phase 2b study, 17 continued in the open-label extension. Patients receiving rhHNS IT 45 mg continued to receive the same treatment regimen (i.e., every 2 weeks or every 4 weeks) throughout the extension. Patients receiving no treatment in the phase 2b study were re-randomized to the treatment groups. Neurocognition was assessed using the Bayley Scales of Infant and Toddler Development®, Third Edition (BSID-III). Adverse events were recorded over the duration of the treatment period. Cognitive decline was observed in most patients in both treatment groups; however, improvements in BSID-III development quotient score were observed for two patients, in receptive and expressive communication scores for three patients each, in fine motor skills for one patient, and in gross motor skills for six patients. Treatment-emergent adverse events that occurred with rhHNS IT were mostly mild, none led to study discontinuation, and there were no deaths. The extension study was terminated early as the primary endpoints of the phase 2b study were not met, and no statistical analyses were carried out. Although cognitive decline was apparent in most patients, improvements were observed in a small group of patients. Greater declines were observed in patients at the higher end of the age range, suggesting earlier intervention may increase the possibility of a response to treatment. rhHNS IT treatment remained generally well tolerated up to 96 weeks.

2019-02-01·Molecular Genetics and Metabolism

Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial

Article

作者: Gasperini, Serena ; Shapiro, Elsa ; Wijburg, Frits A ; Del Toro, Mireia ; Muschol, Nicole ; Kerr, Douglas ; Whitley, Chester B ; Muenzer, Joseph ; Bhargava, Parul ; Alexanderian, David ; Cleary, Maureen ; Sevin, Caroline

BACKGROUNDSanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate in the central nervous system and is associated with progressive neurodegeneration in early childhood. We report on the efficacy, pharmacokinetics, safety, and tolerability of intrathecal (IT) administration of recombinant human HNS (rhHNS) from a phase IIb randomized open-label trial.METHODSTwenty-one patients, randomized 1:1:1 to rhHNS IT 45 mg administered every 2 weeks (Q2W), every 4 weeks (Q4W), or no treatment, were assessed for amelioration in neurocognitive decline as determined by the Bayley Scales of Infant and Toddler Development®, Third Edition. The primary efficacy goal was defined as ≤10-point decline (responder) in at least three patients in a dosing cohort after 48 weeks. Other efficacy assessments included adaptive behavioral function, assessments of cortical gray matter volume, and glycosaminoglycan (GAG) levels in urine.RESULTSA clinical response to rhHNS IT was observed in three treated patients (two in the Q2W group, one in the Q4W group). Cerebrospinal fluid heparan sulfate and urine GAG levels were reduced in all treated patients. However, most secondary efficacy assessments were similar between treated patients (n = 14; age, 17.8-47.8 months) and untreated controls (n = 7; age, 12.6-45.0 months). Treatment-emergent adverse events that occurred with rhHNS IT were mostly mild, none led to study discontinuation, and there were no deaths.CONCLUSIONrhHNS IT treatment reduced heparan sulfate and GAG levels in treated patients. Though the primary neurocognitive endpoint was not met, important lessons in the design and endpoints for evaluation of cognitive and behavioral diseases resulted.TRIAL REGISTRATIONClinicalTrials.govNCT02060526; EudraCT 2013-003450-24.

100 项与 SHP-610 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2期	德国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	美国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	法国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	法国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	德国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	荷兰	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	美国	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	阿根廷	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	荷兰	Shire Plc	2014-02-26
黏多醣贮积症III型	临床2期	阿根廷	Shire Plc	2014-02-26

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临床结果

适应症

分期

评价

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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


NCT01299727 (CTgov)	临床1/2期	黏多醣贮积症III型	12	HGT-1410 (HGT-1410/rhHNS 10 mg)	遞簾觸觸糧窪簾蓋願壓(餘製憲選壓鏇蓋鑰構窪) = 壓襯鑰廠壓糧廠壓製構築糧蓋鹹廠鏇蓋蓋獵膚 (糧夢鬱膚鹹醖積顧觸積, 鏇艱獵獵範獵餘衊範廠 ~ 網築網鏇衊鹽餘衊鹹夢) 更多	-	2020-04-21
				HGT-1410 (HGT-1410/rhHNS 45 mg)	遞簾觸觸糧窪簾蓋願壓(餘製憲選壓鏇蓋鑰構窪) = 廠餘淵壓簾簾糧艱廠鬱築糧蓋鹹廠鏇蓋蓋獵膚 (糧夢鬱膚鹹醖積顧觸積, 築襯齋襯衊齋網壓淵製 ~ 選膚糧憲衊夢廠齋齋醖) 更多
NCT02350816 (CTgov)	临床2期	黏多醣贮积症III型	17	HGT+HGT-1410 (Group 1)	壓壓積膚範艱鹽願窪願(夢鏇夢餘繭憲鹹製艱積) = 廠製齋壓鏇觸築鏇選鏇鹹壓構鹽鹹鑰蓋獵鏇願 (鑰糧餘願醖遞餘繭憲網, 觸鹹構膚廠淵願襯選鏇 ~ 積鏇鹹構蓋鏇網衊積鏇) 更多	-	2020-04-20
				HGT-1410 (Group 2)	壓壓積膚範艱鹽願窪願(夢鏇夢餘繭憲鹹製艱積) = 構淵製鏇顧糧構蓋製願鹹壓構鹽鹹鑰蓋獵鏇願 (鑰糧餘願醖遞餘繭憲網, 遞鏇積憲廠淵壓鏇糧糧 ~ 鹽選艱範製顧鏇顧窪壓) 更多
NCT02060526 (CTgov)	临床2期	黏多醣贮积症III型	21	HGT-1410 (No HGT-1410)	網顧積憲壓繭醖網鏇繭(齋網範選鹹淵齋觸鏇醖) = 艱範艱獵醖鬱製餘憲構夢鏇窪鏇衊獵淵艱淵築 (簾廠餘鹹構齋夢鬱積網, 衊淵蓋繭餘積觸餘願鹹 ~ 構餘觸範壓簾憲廠觸憲) 更多	-	2017-03-03
				HGT-1410 (HGT-1410 45 mg Q2W)	網顧積憲壓繭醖網鏇繭(齋網範選鹹淵齋觸鏇醖) = 簾鬱窪顧鹹鹽醖製鏇夢夢鏇窪鏇衊獵淵艱淵築 (簾廠餘鹹構齋夢鬱積網, 糧網鬱糧窪選築網齋餘 ~ 簾範築糧積廠選積廠遞) 更多