卡德凝血素(Catridecacog) - 药物靶点：fibrin_在研适应症：凝血因子XIII缺乏症，因子Xiii亚基缺乏，出血_专利_临床

概要

基本信息

药物类型

重组凝血因子

别名

Blood Coagulation Factor XIII (Synthetic Human A-Chain Precursor)、Catridecacog (Genetical Recombination)、Catridecacog (INN)

+ [18]

靶点

fibrin

作用机制

fibrin调节剂(纤维蛋白调节剂)、凝血途径激活剂

治疗领域

遗传病与畸形血液及淋巴系统疾病其他疾病

在研适应症

凝血因子XIII缺乏症因子Xiii亚基缺乏出血

非在研适应症

溃疡性结肠炎凝血因子X缺乏症心脏病+ [1]

原研机构

Novo Nordisk A/S

在研机构

Novo Nordisk A/S

Tokyo Medical UniversityNovo Nordisk, Inc.

+ [3]

非在研机构-

最高研发阶段批准上市

首次获批日期

欧盟 (2012-09-03),

因子Xiii亚基缺乏出血

最高研发阶段(中国)-

特殊审评孤儿药 (日本)

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结构/序列

Sequence Code 140469735

来源: *****

关联

17

项与卡德凝血素相关的临床试验

NCT02670213

/ Enrolling by invitationN/A

A Multicentre, Non-interventional Post Marketing Study of Safety and Effectiveness of NovoThirteenR (rFXIII) During Treatment of Congenital FXIII Deficiency in Japan

This study is conducted in Asia. Tha aim of this study is to investigate Safety and Effectiveness of NovoThirteen® (rFXIII) during treatment of congenital FXIII deficiency in Japan.

开始日期2016-03-16

申办/合作机构

Novo Nordisk A/S

NCT01862367

/ CompletedN/A

Use of rFXIII in Treatment of Congenital FXIII Deficiency, a Prospective Multi-centre Observational Study

This study is conducted globally. The aim of this observational study is to investigate the incidence of specific adverse drug reactions associated with the use of recombinant factor XIII (NovoThirteen®) in patients with congenital FXIII A-subunit deficiency (congenital FXIII deficiency), comprising FXIII antibodies, allergic reactions, embolic and thrombotic events and lack of therapeutic effect.
The study will aim at observing all patients exposed to NovoThirteen® in the EU, and additional patients from selected non-EU countries. Recombinant FXIII (rFXIII) is registered in EU and Switzerland as NovoThirteen® and in Canada as Tretten®.

开始日期2013-05-17

申办/合作机构

Novo Nordisk A/S

NCT01706159

/ Terminated临床2期

A Multicenter, Randomised, Double-blind, Placebo-controlled, Multiple-dose Trial With rFXIII Administered to Subjects With Mild to Moderate Active Ulcerative Colitis

This trial is conducted in Europe. The aim of the trial is to investigate the effect of recombinant factor XIII (rFXIII) administered to subjects with mild to moderate active ulcerative colitis (UC).

开始日期2012-10-01

申办/合作机构

Novo Nordisk A/S

100 项与卡德凝血素相关的临床结果

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100 项与卡德凝血素相关的转化医学

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100 项与卡德凝血素相关的专利（医药）

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73

项与卡德凝血素相关的文献（医药）

2024-10-01·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

Development and Epitope Mapping of Seven Mouse Anti-Human Coagulation Factor XIII-B Subunit Monoclonal Antibodies

Article

作者: Magari, Yasuo ; Ichinose, Akitada ; Osaki, Tsukasa ; Souri, Masayoshi

Coagulation factor XIII (FXIII) is an enzyme that strengthens hemostatic clots, and its deficiency can cause life-threatening bleeding. We immunized mice with human plasma-derived FXIII to generate monoclonal antibodies (mAbs) against the B subunit (FXIII-B), which stabilizes the A subunit (FXIII-A) of FXIII, and analyzed their properties. The epitopes of the seven mouse antihuman FXIII-B mAbs obtained were found to be the 3rd, 5th, 6th, 9th, and 10th Sushi domains. One of these mAbs, mAb 5-6C, recognized the 10th Sushi domain and inhibited the fibrin cross-linking reaction without affecting the amine incorporation activity of FXIII. We previously reported that the 10th Sushi domain is the site where FXIII-B binds to fibrin and functions to bring FXIII-A closer to the substrate fibrin. Except for mAb 5-6C, mouse mAbs with high yields were used to measure the amount of FXIII-B antigen by an immunochromatography test (ICT), which showed a high correlation with enzyme-linked immunosorbent assay-obtained results. In addition, we developed a prototype ICT to detect anti-FXIII-B autoantibodies using mAb 1-3C, which showed good results in measuring the amount of FXIII-B antigen. Thus, mouse mAbs may be useful for clinical applications. mAb 5-6C targeting the 10th Sushi domain may also be useful for inhibiting thrombosis progression when humanized as antibody medicines.

2024-07-01·Protein Expression and Purification

Design and construction of a phage-displayed Camelid nanobody library using a simple bioinformatics method

Article

作者: Saffarioun, Mohammad ; Askari, Hooman ; Rahimian, Aliasghar ; Aminian, Mahdi ; Nabati, Ali

BACKGROUNDRational design of synthetic phage-displayed libraries requires the identification of the most appropriate positions for randomization using defined amino acid sets to recapitulate the natural occurrence. The present study uses position-specific scoring matrixes (PSSMs) for identifying and randomizing Camelidae nanobody (VHH) CDR3. The functionality of a synthetic VHH repertoire designed by this method was tested for discovering new VHH binders to recombinant coagulation factor VII (rfVII).METHODSBased on PSSM analysis, the CDR3 of cAbBCII10 VHH framework was identified, and a set of amino acids for the substitution of each PSSM-CDR3 position was defined. Using the Rosetta design SwiftLib tool, the final repertoire was back-translated to a degenerate nucleotide sequence. A synthetic phage-displayed library was constructed based on this repertoire and screened for anti-rfVII binders.RESULTSA synthetic phage-displayed VHH library with 1 × 10⁸ variants was constructed. Three VHH binders to rfVII were isolated from this library with estimated dissociation constants (K_D) of 1 × 10^-8 M, 5.8 × 10^-8 M and 2.6 × 10^-⁷ M.CONCLUSIONPSSM analysis is a simple and efficient way to design synthetic phage-displayed libraries.

2024-02-01·Blood

Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration

Article

作者: Kangro, Kadri ; Kerlin, Bryce A. ; Wolberg, Alisa S. ; Campbell, Robert A. ; Sharaby, Sherif ; Homeister, Jonathon W. ; Holle, Lori A. ; Byrnes, James R. ; Luo, Michelle ; Dobson, Dre’Von A. ; Aleman, Maria M. ; Dumond, Julie B. ; Luyendyk, James P. ; Lee, Taek

AbstractTransglutaminase factor XIII (FXIII) is essential for hemostasis, wound healing, and pregnancy maintenance. Plasma FXIII is composed of A and B subunit dimers synthesized in cells of hematopoietic origin and hepatocytes, respectively. The subunits associate tightly in circulation as FXIII-A2B2. FXIII-B2 stabilizes the (pro)active site-containing FXIII-A subunits. Interestingly, people with genetic FXIII-A deficiency have decreased FXIII-B2, and therapeutic infusion of recombinant FXIII-A2 (rFXIII-A2) increases FXIII-B2, suggesting FXIII-A regulates FXIII-B secretion, production, and/or clearance. We analyzed humans and mice with genetic FXIII-A deficiency and developed a mouse model of rFXIII-A2 infusion to define mechanisms mediating plasma FXIII-B levels. Like humans with FXIII-A deficiency, mice with genetic FXIII-A deficiency had reduced circulating FXIII-B2, and infusion of FXIII-A2 increased FXIII-B2. FXIII-A-deficient mice had normal hepatic function and did not store FXIII-B in liver, indicating FXIII-A does not mediate FXIII-B secretion. Transcriptional analysis and polysome profiling indicated similar F13b levels and ribosome occupancy in FXIII-A-sufficient and -deficient mice and in FXIII-A-deficient mice infused with rFXIII-A2, indicating FXIII-A does not induce de novo FXIII-B synthesis. Unexpectedly, pharmacokinetic/pharmacodynamic modeling of FXIII-B antigen after rFXIII-A2 infusion in humans and mice suggested FXIII-A2 slows FXIII-B2 loss from plasma. Accordingly, comparison of free FXIII-B2 vs FXIII-A2-complexed FXIII-B2 (FXIII-A2B2) infused into mice revealed faster clearance of free FXIII-B2. These data show FXIII-A2 prevents FXIII-B2 loss from circulation and establish the mechanism underlying FXIII-B2 behavior in FXIII-A deficiency and during rFXIII-A2 therapy. Our findings reveal a unique, reciprocal relationship between independently synthesized subunits that mediate an essential hemostatic protein in circulation. This trial was registered at www.ClinicalTrials.com as #NCT00978380.

1

项与卡德凝血素相关的新闻（医药）

2022-09-01

·BioSpace

Novo Nordisk Shells Out $1.1B for Forma, Sickle Cell Drug

Novo Nordisk has entered into an agreement to acquire Forma Therapeutics for $1.1 billion, the company announced Thursday. The deal includes Forma’s lead development candidate, etavopivat. The drug is being assessed in the Phase II GLADIOLUS trial in patients with transfusion-dependent sickle cell disease (SCD) and thalassemia and in the Phase II/III HIBISCUS trial in SCD. Etavopivat is an oral, once-daily, selective pyruvate kinase-R (PKR) activator. It is being developed for anemia and red blood cell health in SCD patients. "By adding Forma’s differentiated approach to address unmet needs for patients, we are taking a step forward in enhancing our sickle cell disease pipeline," said Ludovic Helfgott, EVP and head of rare disease at Novo Nordisk, in a statement. Novo Nordisk is better known for its diabetes and obesity products, including Tresiba, Rybelsus, Victoza and Ozempic. It also has marketed products for hemophilia, such as NovoSeven (recombinant factor VIIa), Esperoct (turoctocog alfa pegol, N8-GP) and NovoThirteen (recombinant factor XIII). Frank D. Lee, president and CEO of Forma, called the announcement "an exciting milestone". “Novo Nordisk will partner closely with the sickle cell community to amplify our impact for patients around the world who urgently need new treatment options," he said in a statement. Forma’s board has unanimously approved the deal, which is expected to close in the fourth quarter of this year. In an email to BioSpace, Novo Nordisk said, "Novo Nordisk has a strong heritage and commitment of 40 years in rare blood disorders, initially within hemophilia and expanding to other rare blood disorders. The acquisition of Forma Therapeutics, including its lead candidate etavopivat, enriches and accelerates the development of Novo Nordisk's preclinical and clinical pipeline in haemoglobinopathies such as sickle cell disease and thalassemia." The deal is for $20 per share in cash, a total equity value of $1.1 billion. This amounts to a 92% premium for Forma’s volume-weighted average price per share over the last 30 days ending August 31. Forma also has programs underway in prostate cancer, acute myeloid leukemia and glioma and preclinical programs in hematological diseases and cancer. On August 2, Forma signed an exclusive, worldwide license deal with Rigel Pharmaceuticals for olutasidenib for relapsed or refractory acute myeloid leukemia. The FDA has accepted Forma’s New Drug Application for the drug with a target action date of February 15, 2023. Rigel paid Forma $2 million upfront. Forma is eligible for another $17.5 million based on various milestone payments, as well as future development and commercial milestones of $215.5 million and tiered royalties in the low-teens to mid-thirties.

并购

100 项与卡德凝血素相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10532	卡德凝血素	B02BD11	DB09310

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
凝血因子XIII缺乏症	瑞士	Novo Nordisk Pharma AG	2012-10-25
因子Xiii亚基缺乏	挪威	Novo Nordisk A/S	2012-09-03
因子Xiii亚基缺乏	冰岛	Novo Nordisk A/S	2012-09-03
因子Xiii亚基缺乏	列支敦士登	Novo Nordisk A/S	2012-09-03
因子Xiii亚基缺乏	欧盟	Novo Nordisk A/S	2012-09-03
出血	欧盟	Novo Nordisk A/S	2012-09-03
出血	挪威	Novo Nordisk A/S	2012-09-03
出血	冰岛	Novo Nordisk A/S	2012-09-03
出血	列支敦士登	Novo Nordisk A/S	2012-09-03

未上市

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
凝血因子XIII缺乏症	药物发现	美国	Novo Nordisk A/S	2008-08-01
凝血因子XIII缺乏症	药物发现	德国	Novo Nordisk A/S	2008-08-01
凝血因子XIII缺乏症	药物发现	西班牙	Novo Nordisk A/S	2008-08-01
凝血因子XIII缺乏症	药物发现	奥地利	Novo Nordisk A/S	2008-08-01
凝血因子XIII缺乏症	药物发现	意大利	Novo Nordisk A/S	2008-08-01
凝血因子XIII缺乏症	药物发现	以色列	Novo Nordisk A/S	2008-08-01
出血	药物发现	美国	Novo Nordisk A/S	2008-08-01
出血	药物发现	以色列	Novo Nordisk A/S	2008-08-01
出血	药物发现	加拿大	Novo Nordisk A/S	2008-08-01
出血	药物发现	瑞士	Novo Nordisk A/S	2008-08-01

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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


NCT01862367 (Pubmed) 人工标引	N/A	凝血因子XIII缺乏症	30	Catridecacog	(窪艱顧網廠餘鹽艱製觸) = All 10 SAEs were unlikely related to rFXIII-A2 鹹壓鏇衊網衊觸鹹積鹽 (獵廠膚築遞窪餘餘窪衊 ) 更多	积极	2022-02-27
ISTH2021	N/A	凝血因子XIII缺乏症	20	catridecacog	醖憲艱蓋艱積餘鬱築製(齋範蓋齋觸鹽艱蓋鏇積) = 醖蓋膚鹹廠齋積獵繭鹹膚窪獵遞顧憲淵餘獵窪 (製獵顧構艱廠鹽壓鑰醖 ) 更多	积极	2021-07-17
ISTH2020	临床4期	因子Xiii亚基缺乏	-	rFXIII-A2	(觸鹹觸願蓋淵觸夢艱鏇) = 艱餘積壓鹽齋積襯廠構窪鹹襯艱衊淵窪艱窪遞 (鑰艱鑰鑰膚獵築壓築繭 )	-	2020-07-12
ISTH2020	N/A	凝血因子XIII缺乏症	17	rFXIII (Catridecacog)	糧網餘蓋憲製觸膚鹹願(壓築艱襯窪繭壓襯鹹網) = The efficacy and safety of rFXIII, used in most cases at the recommended dosage and frequency, was proven in all treated patients 構壓蓋壓鬱鏇構窪積遞 (夢艱鬱選壓積簾鑰網壓 ) 更多	-	2020-07-12
NCT00978380 (Pubmed \| Thromb Haemost) 人工标引	临床3期	因子Xiii亚基缺乏	60	rFXIII-A2	(廠獵範鏇獵顧鹹憲齋憲) = without any safety concerns 壓餘窪積繭構鹽網鬱艱 (淵獵鬱憲積憲積糧艱艱 ) 更多	积极	2018-03-01
NCT01253811 (mentor™5, Pubmed \| J Thromb Haemost) 人工标引	临床3期	营养不良	6	Catridecacog	(艱壓淵憲窪廠築鹹築顧) = Two serious adverse events, unrelated to rFXIII, were reported in a single child, each related to head injury, and neither resulting in intracranial hemorrhage. 窪築選艱願鑰獵構廠艱 (積廠醖顧願選顧襯鑰築 ) 更多	积极	2017-08-01
NCT00978380 (mentor™2 \| mentor(™) 2, CTgov)	临床3期	凝血因子XIII缺乏症	63	Recombinant Factor XIII (rFXIII) (Recombinant Factor XIII (rFXIII))	(獵膚齋製淵艱壓淵壓鑰) = 鏇築壓衊築蓋艱鹹顧範觸積齋觸壓艱憲淵餘顧 (獵製獵艱淵齋網願鹹艱, 觸窪選憲選構齋糧觸鹹 ~ 夢鹽網繭膚憲窪鹽繭蓋) 更多	-	2016-12-13
NCT00978380 (mentor™2 \| mentor(™) 2, CTgov)	临床3期	凝血因子XIII缺乏症	63	rFXIII Novo Nordisk+rFXIII (rFXIII Novo Nordisk)	鏇夢構廠艱糧顧獵膚網(夢繭憲窪艱蓋觸鏇夢範) = 築衊淵顧獵獵廠窪鹽鏇齋鹹製觸蓋鹽齋繭獵鹹 (壓餘鏇襯糧構遞膚窪憲, 淵鬱構築觸遞選齋遞積 ~ 醖蓋蓋鹽衊壓餘築選製) 更多	-	2016-12-13
NCT01253811 (mentor™5, CTgov)	临床3期	因子Xiii亚基缺乏	6	catridecacog	(觸遞膚衊廠獵鬱齋膚淵) = 構願繭範齋網夢鹹鬱糧膚觸簾鏇齋鹽簾顧蓋齋 (糧艱積簾齋齋積廠淵夢, 蓋願築齋製蓋願簾壓範 ~ 獵選鏇鑰襯築構蓋選鹹) 更多	-	2016-06-24
NCT00914589 (CTgov)	临床2期	心脏病 \| 凝血障碍	479	placebo (Placebo)	廠蓋鏇衊獵廠鹹觸齋憲(夢積構繭網簾構醖鏇觸) = 鹽範繭鏇齋壓衊艱範範餘鹽簾餘壓衊蓋襯蓋觸 (艱繭膚膚齋繭範選鹹鏇, 製淵網窪憲鏇糧膚繭齋 ~ 夢鏇糧衊艱構鏇獵淵選) 更多	-	2014-11-13
NCT00914589 (CTgov)	临床2期	心脏病 \| 凝血障碍	479	catridecacog (FXIII17.5IU/Kg)	廠蓋鏇衊獵廠鹹觸齋憲(夢積構繭網簾構醖鏇觸) = 蓋鹹醖淵淵廠襯艱觸鹽餘鹽簾餘壓衊蓋襯蓋觸 (艱繭膚膚齋繭範選鹹鏇, 衊蓋糧憲鑰觸鬱獵範壓 ~ 齋繭構窪鹽遞鹽觸獵糧) 更多	-	2014-11-13
NCT01706159 (CTgov)	临床2期	炎症 \| 溃疡性结肠炎	20	catridecacog (rFXIII)	觸餘鑰壓繭鹹壓鬱鑰築(糧餘簾製願鏇壓顧觸觸) = 廠鬱鬱製繭窪壓鑰鬱窪顧膚簾鬱願製鑰積襯蓋 (鑰鹹醖蓋淵夢顧顧糧蓋, 範鬱獵鑰鏇範遞範衊獵 ~ 鏇壓齋蓋製淵鏇鹹範壓) 更多	-	2014-08-05
NCT01706159 (CTgov)	临床2期	炎症 \| 溃疡性结肠炎	20	placebo (Placebo)	觸餘鑰壓繭鹹壓鬱鑰築(糧餘簾製願鏇壓顧觸觸) = 蓋遞膚積願積選獵膚夢顧膚簾鬱願製鑰積襯蓋 (鑰鹹醖蓋淵夢顧顧糧蓋, 觸製壓餘鬱鏇糧淵鑰醖 ~ 鬱艱簾簾齋鬱鬱選繭簾) 更多	-	2014-08-05