rhIGF-1/rhIGFBP-3(Takeda)(rhIGF-1/rhIGFBP-3(Takeda))

概要

基本信息

药物类型

激素

别名-

靶点-

作用机制-

治疗领域-

在研适应症-

非在研适应症-

原研机构

Shire Plc

在研机构-

非在研机构

Shire Plc

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

2

项与 rhIGF-1/rhIGFBP-3(Takeda) 相关的临床试验

NCT00351221 / Terminated临床2期

A Phase 2, Open-Label, Multicenter, Clinical Trial to Evaluate the Pharmacokinetics, Safety and Efficacy of Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 in Children With Growth Failure Due to Noonan Syndrome

The trial will investigate the treatment of growth failure in children with Noonan syndrome. Abnormalities in the growth hormone (GH) - insulin-like growth factor-I (IGF-I) axis resulting in low IGF-I levels have been suggested as a possible cause of short stature seen in Noonan syndrome children. Administration of our investigational product is intended to bypass the abnormalities in the GH-IGF axis, and hopefully improve body growth.

开始日期-

申办/合作机构

Insmed, Inc.

NCT02386839 / Completed临床2期

Long-term Outcome of Children Enrolled in Study ROPP-2008-01 Previously Treated With rhIGF-1/rhIGFBP-3 for the Prevention of Retinopathy of Prematurity (ROP) or Who Received Standard Neonatal Care

The main purpose of this study is to evaluate the long-term efficacy and safety outcomes following short-term exposure to rhIGF-1/rhIGFBP-3 versus standard neonatal care in Study ROPP-2008-01 (NCT01096784).

开始日期2015-03-26

申办/合作机构

Shire Plc

100 项与 rhIGF-1/rhIGFBP-3(Takeda) 相关的临床结果

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100 项与 rhIGF-1/rhIGFBP-3(Takeda) 相关的转化医学

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100 项与 rhIGF-1/rhIGFBP-3(Takeda) 相关的专利（医药）

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22

项与 rhIGF-1/rhIGFBP-3(Takeda) 相关的文献（医药）

2024-06-01·Pediatric Research

Recombinant IGF-1/BP3 protects against intestinal injury in a neonatal mouse NEC model

Article

作者: Managlia, Elizabeth ; Tan, Xiao-Di ; Barton, Norman ; Carey, Galen ; Yan, Xiaocai ; De Plaen, Isabelle G

BACKGROUNDRecombinant human IGF-1/binding protein-3 (rhIGF-1/BP3) is currently being tested in phase II clinical trials in premature infants to prevent bronchopulmonary dysplasia, but its impact on the neonatal intestine remains unclear. The aim of this study was to determine whether rhIGF-1/BP3 protects against necrotizing enterocolitis (NEC) in mice and to investigate the mechanisms involved.METHODSNeonatal mice were dam fed or injected intraperitoneally with rhIGF-1/BP3 (or vehicle) and submitted to an experimental NEC model. Serum IGF-1 was assessed by ELISA and intestinal vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression by Western blot. Intestinal endothelial cell proliferation, and enterocyte proliferation and migration were examined by immunofluorescence. Pup survival and histological intestinal injury were determined.RESULTSIn pups exposed to experimental NEC, serum IBP3-bound IGF-1 level was decreased. Exogenous rhIGF-1/BP3 preserved VEGF and VEGFR2 protein expression, decreased vascular permeability, and preserved endothelial cell proliferation in the small intestine. Furthermore, rhIGF-1/BP3 promoted enterocyte proliferation and migration, which effects were attenuated by inhibiting VEGFR2 signaling, decreased enterocyte apoptosis and decreased systemic and intestinal inflammation. rhIGF-1/BP3 improved survival and reduced the incidence of severe intestinal injury in experimental NEC.CONCLUSIONSExogenous rhIGF-1/BP3 protects neonatal mice against experimental NEC via multiple mechanisms.IMPACTExogenous rhIGF-1/BP3 preserves intestinal microvascular development and integrity, promotes enterocyte proliferation and migration, decreases local and systemic inflammation, and protects neonatal mice against NEC. The article adds pre-clinical evidence of a protective role for rhIGF-1/BP3 on the premature gut. It provides evidence supporting the use of rhIGF1/BP3 in premature neonates to protect against NEC.

2023-06-15·BMC pulmonary medicine

The role of rhIGF-1/BP3 in the prevention of pulmonary hypertension in bronchopulmonary dysplasia and its underlying mechanism.

Article

作者: Dong, Huaifu ; Zhuo, Feixiang ; Chen, Yun ; Wu, Yumeng ; Shan, Lianqiang ; Chen, Xin ; Wang, Yitong ; Qu, Sehua ; Zhang, Zhen

BACKGROUNDThis study aimed to determine whether postnatal treatment with recombinant human IGF-1 (rhIGF-1)/binding peptide 3 (BP3) ameliorates lung injury and prevents pulmonary hypertension (PH) in bronchopulmonary dysplasia (BPD) models.METHODSWe used two models of BPD in this study: one model that was associated with chorioamnionitis (CA), stimulated by intra-amniotic fluid and exposure to lipopolysaccharide (LPS), whereas the other was exposed to postnatal hyperoxia. Newborn rats were treated with rhIGF-1/BP3 (0.2 mg/Kg/d) or saline via intraperitoneal injection. The study endpoints included the wet/dry weight (W/D) ratio of lung tissues, radial alveolar counts (RACs), vessel density, right ventricular hypertrophy (RVH), lung resistance, and lung compliance. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the degree of lung injury and pulmonary fibrosis. IGF-1 and eNOS expression were detected using western blotting or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The levels of SP-C, E-cadherin, N-cadherin, FSP1, and Vimentin in the lung tissues were detected by immunofluorescence.RESULTSLPS and hyperoxia treatment increased lung injury and pulmonary fibrosis, enhanced RVH and total respiratory resistance, and decreased RAC, pulmonary vascular density and pulmonary compliance in young mice (all p < 0.01). Simultaneously, LPS and hyperoxia induced an increase in epithelial-mesenchymal transition (EMT) in airway epithelial cells. However, rhIGF-1/BP3 treatment reduced lung injury and pulmonary fibrosis, decreased RVH and total respiratory resistance, and enhanced RAC, pulmonary vascular density and pulmonary compliance, as well as inhibited EMT in airway epithelial cells in LPS and hyperoxia treated mice.CONCLUSIONPostnatal rhIGF-1/BP3 treatment relieved the effects of LPS or hyperoxia on lung injury and prevented RVH, providing a promising strategy for the treatment of BPD.

2022-05-01·Journal of Pharmaceutical Sciences3区 · 医学

Development of Protein-Specific Analytical Methodologies to Evaluate Compatibility of Recombinant Human (rh)IGF-1/rhIGFBP-3 with Intravenous Medications Co-Administered to Neonates

3区 · 医学

Article

作者: Qu, Wanlu ; McPherson, Christopher ; Salamat-Miller, Nazila ; Salinas, Paul A ; Barton, Norman ; Chadwick, Jennifer S ; Wang, Dongdong ; Turner, Mark

The protein complex of recombinant human insulin-like growth factor-1 and insulin‑like growth factor binding protein‑3 (rhIGF-1/rhIGFBP-3; mecasermin rinfabate), is an investigational product for the prevention of complications of prematurity. Delivery of rhIGF-1/rhIGFBP-3 is by continuous central line intravenous infusion in preterm infants until endogenous IGF-1 production begins. Protein-specific analytical methodologies were developed to evaluate the compatibility of rhIGF-1/rhIGFBP-3 at low protein concentrations (∼2.5-10 μg/mL) expected when co-administered with other required medications in the NICU. Highly sensitive detection of the biologic potential degradants (fragments) and/or molecular modifications (oxidized species, aggregates) required the use of reversed-phase high-performance liquid chromatography and size-exclusion ultra-performance liquid chromatography coupled with mass spectrometric detection. We report on the quantification of rhIGF-1/rhIGFBP-3, its components and degradants, to a limit of quantitation of 3.1 μg/mL upon mixing with 24 commonly administered neonatal medications. Methods developed for the rhIGF-1/rhIGFBP-3 admixtures, optimized in studies with furosemide, caffeine citrate and ampicillin, demonstrated good reproducibility, linearity, and limit of detection/quantitation. Using these methods, no increase in degradation of rhIGF-1/rhIGFBP-3 components and no increase in oxidation or aggregation level was observed with caffeine citrate, while admixtures of rhIGF-1/rhIGFBP-3 with ampicillin yielded lower mass recovery of rhIGF-1/rhIGFBP-3 components, which likely resulted from adduct formation. Furosemide was found to be physically incompatible with rhIGF-1/rhIGFBP-3. Our findings support the use of these methodologies for detection of protein modifications under various clinical administration conditions, and additionally supplement physical compatibility data studies of ultra-low concentrations of rhIGF-1/rhIGFBP-3 post co-administration to preterm infants with other medications (manuscript in-preparation).

100 项与 rhIGF-1/rhIGFBP-3(Takeda) 相关的药物交易

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研发状态

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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


NCT02386839 (PEDAL, CTgov)	临床2期	早产儿视网膜病变	76	rhIGF-1/rhIGFBP-3 (Antecedent Standard of Care)	鏇襯餘選鏇餘膚壓鹽範(顧膚憲選壓艱餘膚衊夢) = 淵選糧製餘鬱遞廠網繭積繭鏇襯鏇選鹽繭製糧 (壓鑰鏇簾壓願範願衊淵, 襯窪製鹽鹹構鏇淵夢鏇 ~ 膚構製憲範鹽範觸艱壓) 更多	-	2022-04-25
				rhIGF-1/rhIGFBP-3 (Antecedent rhIGF-1/rhIGFBP-3)	鏇襯餘選鏇餘膚壓鹽範(顧膚憲選壓艱餘膚衊夢) = 蓋觸鹽簾鹽壓範網齋製積繭鏇襯鏇選鹽繭製糧 (壓鑰鏇簾壓願範願衊淵, 鏇鬱衊齋鏇窪餘簾廠製 ~ 窪廠願鹹壓範觸築製積) 更多
ERS2017	临床2期	支气管肺发育不良	121	rhIGF-1/rhIGFBP-3	(壓淵鏇襯積築構願獵觸) = 艱夢鑰蓋鹹夢醖構願繭醖鑰築遞壓襯範窪蓋壓 (鬱壓鏇願夢膚鬱願齋鏇 )	-	2017-09-01
				Recombinant human (rh)IGF-1/rhIGFBP-3	(壓淵鏇襯積築構願獵觸) = 製醖觸餘選鏇鏇襯窪糧醖鑰築遞壓襯範窪蓋壓 (鬱壓鏇願夢膚鬱願齋鏇 )
ARVO2016	N/A	早产儿疾病	10	rhIGF-1/rhIGFBP-3	(襯簾網網範鹽簾繭鑰製) = 廠襯築鹽鹽鏇餘鬱範糧衊顧齋襯夢簾選膚觸夢 (顧齋齋夢鏇夢鹽蓋糧鏇 )	-	2016-09-01
				rhIGF-1/rhIGFBP-3	(襯簾網網範鹽簾繭鑰製) = 齋衊範顧觸網鹹廠鹽積衊顧齋襯夢簾選膚觸夢 (顧齋齋夢鏇夢鹽蓋糧鏇 )